lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC1CCN(C(=O)OC(C)(C)C)CC1c1nnn2cnc3[nH]ccc3c12
InChIKey: IVFATVRABARRFI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 356.43, ALogP 2.97, HBA 6, HBD 1, PSA 88.41, QED 0.72
Compound (SMILES): COc1cc(OC)cc(N(CCNC(=O)C2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: ARDLUUQELBPNNT-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 472.55, ALogP 3.71, HBA 8, HBD 1, PSA 94.4, QED 0.4
Compound (SMILES): COc1cc(F)cc(C(=O)N2CCC(N3CC(CC#N)(n4cc(-c5ncnc6[nH]ccc56)cn4)C3)CC2)c1
InChIKey: IJRZRTMNZPOXPD-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 514.57, ALogP 3.2, HBA 8, HBD 1, PSA 115.96, QED 0.42
Compound (SMILES): CCS(=O)(=O)Nc1ccc(OCC(C)(C)C)c(-c2cn(C)c(=O)c3[nH]ccc23)c1
InChIKey: MAEDJUGOIKDPTL-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 in human H1299 cells assessed as decrease in HPV LCR-E2-EP400-mediated transcriptional repression after 24 hrs by Bright-Glo luciferase reporter gene assay
Measurement: EC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 417.53, ALogP 3.72, HBA 5, HBD 2, PSA 93.19, QED 0.64
Compound (SMILES): COc1cc(C#N)ccc1N1CCOc2cc(S(=O)(=O)Nc3nccs3)ccc21
InChIKey: BCCZTFIOURKUIO-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 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 428.5, ALogP 3.35, HBA 8, HBD 1, PSA 104.55, QED 0.66
Compound (SMILES): O=C(O)[C@H]1CC[C@H](C(=O)N2CC[C@](c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3)(S(=O)(=O)c3ccc(F)c(C4CC4)c3)C2)CC1
InChIKey: LWEFWPKVZAGQGI-BATDWUPUSA-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 667.61, ALogP 6.79, HBA 4, HBD 1, PSA 91.75, QED 0.26
Compound (SMILES): COCc1c(-c2cc3cc(C)cc(OC)c3s2)c2c(N)ncnn2c1CN1CCNC(=O)C1
InChIKey: HNLRRJSKGXOYNO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human recombinant FGFR1 in the presence of ATP at 0.16 uM measured after 1 hr by fluorescence based assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 466.57, ALogP 2.59, HBA 9, HBD 2, PSA 107.01, QED 0.45
Compound (SMILES): C=CC(=O)Nc1cccc(-c2cnc3[nH]cc(Cl)c3c2)c1
InChIKey: HUFYIJJOYHBFHQ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
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 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 297.75, ALogP 4.01, HBA 2, HBD 2, PSA 57.78, QED 0.72
Compound (SMILES): O=S(=O)(c1ccc(-c2cn3c4nc(ncc24)NCCCCCCCC(O)CCCC3)cc1)N1CCOCC1
InChIKey: SCCZGJNJWOJDLN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of MerTK (unknown origin) by microfluidic capillary electrophoresis assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 541.72, ALogP 4.42, HBA 8, HBD 2, PSA 109.58, QED 0.51
Compound (SMILES): Cc1nc(C2CCCCC2)c2c3cc[nH]c3ncn12
InChIKey: VEBMETUDINBSIP-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 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 254.34, ALogP 3.57, HBA 3, HBD 1, PSA 45.98, QED 0.72
Compound (SMILES): Cc1cc(NC(=O)N2CCCC(c3nnn4cnc5[nH]ccc5c34)C2)sn1
InChIKey: QGLOJQGSJPZTLN-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 = 560 nM (pChEMBL 6.25)
Descriptors: MW 382.45, ALogP 2.78, HBA 7, HBD 2, PSA 104.1, QED 0.55
Compound (SMILES): CC(O)c1ccc(-c2ccc(-n3cc(C(C)(C)O)nc3C(C)(C)c3ccccc3Cl)cc2)cc1S(C)(=O)=O
InChIKey: KDKLTCKHENMCSN-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Agonist activity at LXR-beta in human HeLa cells assessed as induction of ABCA1 by beta-galactosidase/luciferase reporter gene assay
Measurement: EC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 553.12, ALogP 6.2, HBA 6, HBD 2, PSA 92.42, QED 0.28
Compound (SMILES): COc1ccc(C2=C(C#N)C(=O)NC(c3ccc(OCCCC(F)(F)F)cc3)(C(F)(F)F)C2)cc1
InChIKey: QEMIMKHKUITFJX-UHFFFAOYSA-N
Target: Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q10469
Assay: Inhibition of human recombinant MGAT2 expressed in Sf9 cell membrane using 2-monooleglycerol and [H3]-oleoyl-CoA as substrates incubated for 20 mins by scintillation proximity assay
Measurement: IC50 = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 498.42, ALogP 5.67, HBA 4, HBD 1, PSA 71.35, QED 0.39
Compound (SMILES): Nc1ncc(-c2ccccc2)nc1C(=O)Nc1cnccc1N1CCC(N)CC1
InChIKey: LLMXWBSEQIDLJG-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of GSK-3-beta (unknown origin)
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 389.46, ALogP 2.3, HBA 7, HBD 3, PSA 123.05, QED 0.63
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1csc(-c2ccc(Cl)cc2)n1
InChIKey: KIHIMMDNUNDKTJ-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 543.86, ALogP 8.04, HBA 7, HBD 1, PSA 69.16, QED 0.22
Compound (SMILES): COC(=O)N1CC[C@](C)(N2CCc3c(-c4cnc(N)nc4)nc(N4CCOCC4)nc32)C1
InChIKey: KEPIQLTVJCPYMV-NRFANRHFSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human PI3K p110beta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay
Measurement: Ki = 0.79 nM (pChEMBL 9.100000381469727)
Descriptors: MW 440.51, ALogP 0.95, HBA 10, HBD 1, PSA 122.83, QED 0.74
Compound (SMILES): Cl.c1ccc(N(CC2CC2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)cc1
InChIKey: XRTFMLXFXJOUEC-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 341.42, ALogP 4.57, HBA 4, HBD 1, PSA 57.7, QED 0.58
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC[C@@]3(C[C@H]3c3ccc(F)cc3)C2)n1C
InChIKey: XRDPJIJIWYVCKW-PGRDOPGGSA-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 > 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 427.55, ALogP 4.28, HBA 7, HBD 0, PSA 59.98, QED 0.41
Compound (SMILES): Cc1nnc2sc(C(=O)NCc3ccc(S(=O)(=O)C(F)F)cc3)c(N)c2c1C
InChIKey: KNZAIFIZJGFOCI-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 426.47, ALogP 2.82, HBA 7, HBD 2, PSA 115.04, QED 0.65
Compound (SMILES): O=C(O)C12CCC(C(=O)N3CC[C@](c4ccc(C(F)(C(F)(F)F)C(F)(F)F)cc4)(S(=O)(=O)c4ccc(F)cc4)C3)(CC1)C2
InChIKey: XHTMLUDJBICVHB-STEQJIOHSA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Transactivation of human GAL4-fused LXRalpha expressed in African green monkey CV1 cells
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 639.56, ALogP 6.05, HBA 4, HBD 1, PSA 91.75, QED 0.31
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: XJOQXSSQHKPXSP-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 415.5, ALogP 4.6, HBA 7, HBD 0, PSA 65.3, QED 0.44
Compound (SMILES): CCCOc1ccc(CCc2nc3cc(-c4c(C)noc4C)ccc3n2CCN2CCOCC2)cc1
InChIKey: CGWBJJZOKGZCSJ-UHFFFAOYSA-N
Target: CREB-binding protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q92793
Assay: Inhibition of CREBBP (unknown origin) by FRET assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 488.63, ALogP 5.21, HBA 7, HBD 0, PSA 65.55, QED 0.31
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(F)nc4)cc23)c1F
InChIKey: UBJUBKFKARGYJS-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 474.46, ALogP 4.42, HBA 5, HBD 2, PSA 104.81, QED 0.3
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ccnc(N)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: DBFMFHYDGXJVLJ-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 = 2187.76 nM (pChEMBL 5.659999847412109)
Descriptors: MW 492.54, ALogP 3.61, HBA 10, HBD 1, PSA 117.1, QED 0.35
Compound (SMILES): COc1cc(O)cc(N(CCNC(C)C)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1.Cl
InChIKey: WDACLZKYOGTKNW-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 = 6456.54 nM (pChEMBL 5.190000057220459)
Descriptors: MW 418.5, ALogP 3.87, HBA 7, HBD 3, PSA 99.19, QED 0.4
Compound (SMILES): Cc1cccc(-c2cc(N)nc3[nH]cc(C#N)c23)c1
InChIKey: KWTGXMXCSXFSJX-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of recombinant human GST-tagged LRRK2 G2019S mutant (970 to 2527 residues) expressed in baculovirus using fluorescein-LRRKtide as substrate after 2 hrs by TR-FRET assay
Measurement: Ki = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 248.29, ALogP 2.99, HBA 3, HBD 2, PSA 78.49, QED 0.69
Compound (SMILES): CNCCN1CCC(OCc2ccccc2)CC1
InChIKey: HBOJWAYLSJLULG-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]alpha-methylhistamine from human histamine H3 receptor expressed HEK Flp-In cell membranes
Measurement: Ki = 87 nM (pChEMBL 7.059999942779541)
Descriptors: MW 248.37, ALogP 1.89, HBA 3, HBD 1, PSA 24.5, QED 0.83
Compound (SMILES): COc1cc(N2CCC(C3CCN(CCS(C)(=O)=O)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: YZEQLRRLTUYDIQ-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 820.97, ALogP 7.71, HBA 11, HBD 2, PSA 134.06, QED 0.13
Compound (SMILES): O=C(OCC12CCN(CC1)CC2)c1c[nH]c2cc(F)cc(Br)c12
InChIKey: NCFMFECNCBFFBW-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Cytochrome P450 Inhibition: Protocol 1: Studies were carried out in human liver microsomes. Human liver microsomes were purchased from BD Gentest. DMSO stocks were prepared for the test compounds. Aliquots of the DMSO solutions were diluted 1:3 by acetonitrile:ACN mixture (v/v: 40:60) to "400×" intermediate solutions, then further diluted by liver microsomes/buffer to "2×" intermediate solutions. "2×" intermediate solutions were mixed with "2×" NADPH/substrate solutions, which had been pre-warmed to 37° C. (final test compound concentrations were 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, 0.0136 μM, and 0 μM). The plates were kept in a 37° C. water bath for the duration of the experiment. At the end of incubation (5 minutes for 3A4; 45 minutes for 2C19; 10 minutes for 1A2, 2C9, 2D6), 120 μL of acetonitrile was added into corresponding wells. After the final time point was sampled, the plates were shaken at a vibrator (IKA, MTS 2/4) for 10 mM (600 rpm/min) and then centrifuged at 5594 g for 15 mM (Thermo Multifuge×3R). Aliquots of the supernatant were removed, diluted 1:1 into distilled water, and analyzed by LC-MS/MS. The peak area response ratio to internal standard (PARR) of the compounds at 10 μM, 3.3 μM, 1.1 μM, 0.37 μM, 0.122 μM, 0.041 μM, and 0.0136 μM was compared to the PARR at 0 μM to determine the percent of metabolite generation from substrate at each test compound concentration.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 381.25, ALogP 3.71, HBA 3, HBD 1, PSA 45.33, QED 0.82
Compound (SMILES): COc1nc(N(CC(C)(C)F)c2cc(Cl)c(F)cc2F)cnc1C(=O)[C@H]1C[C@@H]1C(=O)O
InChIKey: RVMWIVNHZMXEHS-UWVGGRQHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of recombinant human CYP3A4 expressed in Escherichia coli using coumarin based substrate by fluorescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 457.84, ALogP 4.21, HBA 6, HBD 1, PSA 92.62, QED 0.47
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4nc(C)n(Cc5ccc(F)cc5)c(=O)c4c3)cc12
InChIKey: VMEBZEMJNJSXPG-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Non-nucleoside inhibition of NS5B polymerase in HCV genotype 4a by Taqman probe based RT-PCR analysis
Measurement: EC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 642.68, ALogP 5.87, HBA 7, HBD 1, PSA 114.51, QED 0.23
Compound (SMILES): COc1cc(OC)cc(N(Cc2csc(C)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: IIGRWRUGUUITMA-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 472.57, ALogP 5.15, HBA 9, HBD 0, PSA 78.19, QED 0.32
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)OCC3CC3)CC2)C1
InChIKey: HWFLJCHMMMZJHB-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 > 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 460.54, ALogP 2.76, HBA 8, HBD 1, PSA 115.96, QED 0.6
Compound (SMILES): COc1cc(N2CCN(CCS(C)(=O)=O)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: ACEREWSFULKZGV-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 738.82, ALogP 5.91, HBA 11, HBD 2, PSA 134.06, QED 0.17
Compound (SMILES): COc1cc(OC)cc(N(CCN2CC[C@H](C#N)C2)c2ccc3ncc(-c4cnn(CC5CCOCC5)c4)nc3c2)c1
InChIKey: FNJXQSFBTXMNDB-XMMPIXPASA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of TEL-fused FGFR3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 72 hrs by Alamar blue assay
Measurement: IC50 = 0.4571 nM (pChEMBL 9.34000015258789)
Descriptors: MW 567.69, ALogP 4.92, HBA 10, HBD 0, PSA 101.56, QED 0.26
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)C3CCC(F)(F)CC3)CC2)C1
InChIKey: HDSRMYGFRHGZPX-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 508.58, ALogP 3.56, HBA 7, HBD 1, PSA 106.73, QED 0.56
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1cc(Br)cc(Br)c1
InChIKey: YETQQFMHUDZVIA-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 584.1, ALogP 7.79, HBA 5, HBD 1, PSA 56.27, QED 0.25
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(Cc3cc(F)cc(F)c3)CC2)C1
InChIKey: SWQZXCPMESABJL-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 488.55, ALogP 3.69, HBA 7, HBD 1, PSA 89.66, QED 0.45
Compound (SMILES): NC(=O)c1cccc([C@H]2C[C@H]3CC[C@@H](C2)N3CCN(CCCc2ccccc2)C(=O)CO)c1
InChIKey: RBEQOHMLGWWJOC-QEIWAGNOSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DPN from recombinant human mu opioid receptor expressed in CHO-K1 cell membranes by radioligand binding assay
Measurement: Ki = 0.7943 nM (pChEMBL 9.100000381469727)
Descriptors: MW 449.6, ALogP 2.95, HBA 4, HBD 2, PSA 86.87, QED 0.58
Compound (SMILES): COc1cc(F)ccc1-c1nc(Nc2cc(F)cc(CS(C)(=N)=O)c2)ncc1F
InChIKey: NSJOYQIOHVHMCZ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: CDK2/CycE Kinase Assay: Recombinant fusion proteins of GST and human CDK2 and of GST and human CycE, expressed in insect cells (Sf9) and purified by Glutathion-Sepharose affinity chromatography, were purchased from ProQinase GmbH (Freiburg, Germany). As substrate for the kinase reaction biotinylated peptide biotin-Ttds-YISPLKSPYKISEG (C-terminus in amid form) was used which can be purchased e.g. form the company JERINI Peptide Technologies (Berlin, Germany)For the assay 50 nl of a 100 fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384 well microtiter plate (Greiner Bio-One, Frickenhausen, Germany), 2 ul of a solution of CDK2/CycE in aqueous assay buffer [50 mM Tris/HCl pH 8.0, 10 mM MgCl2, 1.0 mM dithiothreitol, 0.1 mM sodium ortho-vanadate, 0.01% (v/v) Nonidet-P40 (Sigma)] were added and the mixture was incubated for 15 min at 22 C. to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 422.43, ALogP 4.49, HBA 6, HBD 2, PSA 87.96, QED 0.61
Compound (SMILES): O=C(O)[C@H]1[C@@H]2C[C@@H](C(=O)N3CC[C@](c4ccc(C(F)(C(F)(F)F)C(F)(F)F)cc4)(S(=O)(=O)c4ccc(F)cc4)C3)C[C@@H]21
InChIKey: HNOZQRKROBDUDI-LPSQLEIASA-N
Target: Oxysterols receptor LXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q13133
Assay: Transactivation of human GAL4-fused LXRalpha expressed in African green monkey CV1 cells
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 625.53, ALogP 5.37, HBA 4, HBD 1, PSA 91.75, QED 0.34
Compound (SMILES): Cc1cc(Nc2nc([C@H](O)c3ccc(F)cc3)nc3ccccc23)n[nH]1
InChIKey: DCRWIATZWHLIPN-QGZVFWFLSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Adenosine A3 Receptor Radioligand Binding Assay: .(R)- and (S)-(4-Fluorophenyl)(4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)methanol was tested in a radioligand binding assay, according to the procedure described in Olah et al., Mol. Pharmacol. 1994, 45, 978-982 and Salvatore et al., Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 10365-10369, in human recombinant CHO-K1 cells expressing the human adenosine A3 receptor. Incubations of a range of concentration of each compound were carried out in duplicates for 1 h at 25° C. in 25 mM HEPES, pH 7.4, 5 mM MgCl2, 1 mM CaCl2, 0.1% BSA, in the presence of 0.5 nM [125I] AB-MECA. Non-specific binding was determined in the presence of 1 uM IB-MECA.
Measurement: Kd = 28.5 nM (pChEMBL 7.539999961853027)
Descriptors: MW 349.37, ALogP 3.63, HBA 5, HBD 3, PSA 86.72, QED 0.52
Compound (SMILES): COC(=O)Nc1ccc(S(=O)(=O)C(C)C)c([C@H]2CCCN2C(=O)[C@H](Nc2cc3c(cc2F)CNC3=O)c2ccc(OC)c(OC)c2)c1
InChIKey: BPIJQVAKJCDFPD-PDDLMNHVSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of human thrombin
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 668.74, ALogP 4.96, HBA 9, HBD 3, PSA 152.37, QED 0.27
Compound (SMILES): COc1cc(C(=O)NC(c2ccccc2F)C(C)(C)O)ccc1-c1cn[nH]c1
InChIKey: UHTJASDMENLSNM-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as ROCK inhibitors can be determined in a 30 μL assay containing 20 mM HEPES, pH 7.5, 20 mM MgCl2, 0.015% Brij-35, 4 mM DTT, 5 μM ATP and 1.5 μM peptide substrate (FITC-AHA-AKRRRLSSLRA-OH). Compounds were dissolved in DMSO so that the final concentration of DMSO was <2%, and the reaction was initiated with Rho kinase variants. After incubation, the reaction was terminated by the addition of EDTA and the phosphorylated and non-phosphorylated peptides separated using a LABCHIP® 3000 Reader (Caliper Life Sciences). Controls consisted of assays that did not contain compound, and backgrounds consisted of assays that contained enzyme and substrate but had EDTA from the beginning of the reaction to inhibit kinase activity.
Measurement: IC50 = 2.07 nM (pChEMBL 8.680000305175781)
Descriptors: MW 383.42, ALogP 3.47, HBA 4, HBD 3, PSA 87.24, QED 0.61
Compound (SMILES): COc1nc2ccc(C(O)(c3ccc(Cl)cc3)c3cncn3C)cc2c(Cl)c1Oc1ccccc1
InChIKey: DMNDKESGHYMQPJ-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: RORγt Reporter Assay: The reporter assay was performed by transiently transfecting HEK293T cells with 5 μg of pBIND-RORγt LBD or pBIND-RORγt LBD-AF2 and 5 μg pGL4.31 (Promega Cat no. C935A) using Fugene 6 (Invitrogen Cat no. E2691) at a 1:6 ratio of DNA: Fugene 6 in a T-75 flask in which cells were at least 80% confluent. Twenty four hours after bulk transfection, cells were plated into 96-well plates at 50,000 cells/well in phenol-red free DMEM containing 5% Lipid Reduced FCS and Pen/Strep. Six hours after plating, cells were treated with compounds for 24 hours. Media was removed and cells were lysed with 50 μL 1x Glo Lysis Buffer (Promega). Dual Glo Luciferase Reagent (50 μL/well) was then added and firefly luciferase luminescence was read on an Envision after a ten minute incubation. Finally, Stop and Glo reagent (50 μL/well) was added and renilla luciferase luminescence was read on an Envision after a ten minute incubation.
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 506.39, ALogP 6.36, HBA 6, HBD 1, PSA 69.4, QED 0.29
Compound (SMILES): CC[C@@H]1C[C@](O)(C(F)(F)F)[C@@H](Nc2cccc3[nH]c(=O)ccc23)c2cc(F)c(F)c(O)c21
InChIKey: VZPLUSXTJULLCS-SYQZRHMFSA-N
Target: Mineralocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08235
Assay: Binding affinity to recombinant human mineralocorticoid receptor expressed in baculovirus infected sf9 cells
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 454.39, ALogP 4.86, HBA 4, HBD 4, PSA 85.35, QED 0.43
Compound (SMILES): COc1ccc2[nH]cc(C(=O)OCC34CCN(CC3)CC4)c2c1C
InChIKey: QQUURDHIAIQVBB-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Cytochrome P450 Inhibition: Protocol 2: Stock solution for NCEs (test articles) and standard inhibitors were prepared at a concentration of 20 mM in DMSO. Stock solutions were diluted with DMSO to get substocks which were further diluted 10-fold in 80:20 MeCN:water to obtain intermediate substocks. Working stocks were prepared by diluting the intermediate substocks 50-fold in buffer.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 328.41, ALogP 3.13, HBA 4, HBD 1, PSA 54.56, QED 0.88
Compound (SMILES): COc1cc2c(Nc3ccc(Br)c(Cl)c3F)ncnc2cc1OC[C@@H]1CN2CCC[C@H]2CO1
InChIKey: VEZBREXQDQRJTD-KBPBESRZSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: Inhibition of recombinant human N-terminal GST-tagged factor 10a cleavage site-fused Flt1 (K784 to I1338 residues) expressed in baculovirus infected insect Sf9 cells using poly-EY as substrate after 120 mins in presence of gamma33P-ATP by liquid scintillation spectrometry
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 537.82, ALogP 5.18, HBA 7, HBD 1, PSA 68.74, QED 0.43
Compound (SMILES): COc1cc(O)cc(N(CCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HHRGGSVSAUUCLO-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 391.43, ALogP 2.87, HBA 8, HBD 2, PSA 96.53, QED 0.52
Compound (SMILES): CCOc1cc(F)cc(N(CCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: QCYDLOHINRAHID-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 407.45, ALogP 3.7, HBA 7, HBD 1, PSA 76.3, QED 0.5
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCC(N(C)C)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MZLXXVIDRYUZIM-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 4.21, HBA 9, HBD 0, PSA 71.78, QED 0.33
Compound (SMILES): CC(C)n1nc(-c2ccc3nc(N)oc3c2)c2c(N)ncnc21
InChIKey: KMGZJEWJXAGHOP-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of human PI3Kdelta using PIP2 as substrate by HTRF assay
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 309.33, ALogP 2.38, HBA 8, HBD 2, PSA 121.67, QED 0.58
Compound (SMILES): CCC#CC(=O)Nc1cccc(-c2cnc3[nH]cc(C)c3c2)c1
InChIKey: GNIWWRYROYEXHL-UHFFFAOYSA-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 303.37, ALogP 3.89, HBA 2, HBD 2, PSA 57.78, QED 0.71
Compound (SMILES): COCCNC(=O)C(C)(C)n1cc(-c2cnc3ccc(N(CC4CC4)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: NGLRSTVZLVHSJO-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 544.66, ALogP 4.56, HBA 9, HBD 1, PSA 103.63, QED 0.26
Compound (SMILES): Cc1ncc(NC(=O)c2cccc(C(F)(F)F)c2)cc1-c1cnc(OC2CCOCC2)c(N2CCOCC2)c1
InChIKey: FYNMINFUAIDIFL-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Inhibition of CRAF in human Calu6 cells assessed as decrease in ERK phosphorylation
Measurement: EC50 = 100 nM (pChEMBL 7)
Descriptors: MW 542.56, ALogP 5.12, HBA 7, HBD 1, PSA 85.81, QED 0.46
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCN5CCCC5)c4)nc3c2)c1.Cl
InChIKey: PAWXGXHMRSTMFA-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 498.63, ALogP 5.15, HBA 8, HBD 0, PSA 68.54, QED 0.3
Compound (SMILES): O=c1cc(/C=C/c2ccc(C(F)(F)F)cc2)c2cc(C(c3ccc(Cl)cc3)c3nccs3)ccc2[nH]1
InChIKey: LWHNNHZAUBLVTM-DAFODLJHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam/testosterone as substrate after 10 to 30 mins by LC/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 522.98, ALogP 8.01, HBA 3, HBD 1, PSA 45.75, QED 0.25
Compound (SMILES): CC#CC(=O)Nc1cccc(-c2cnc3[nH]cc(Cl)c3c2)n1
InChIKey: SHWCVOJZLIWKHV-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 310.74, ALogP 3.24, HBA 3, HBD 2, PSA 70.67, QED 0.71
Compound (SMILES): CCC(C(=O)Nc1cc(F)c(C(=O)O)cc1F)n1cc(OC)c(-c2cc(Cl)ccc2C#N)cc1=O
InChIKey: ZVXCULUAQHRZBD-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Measurement of FXIa Inhibition: To determine the factor XIa inhibition of the substances according to the invention, a biochemical test system is used which utilizes the reaction of a peptidic factor XIa substrate to determine the enzymatic activity of human factor XIa. Here, factor XIa cleaves from the peptic factor XIa substrate the C-terminal aminomethylcoumarin (AMC), the fluorescence of which is measured. The determinations are carried out in microtitre plates.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 of Tris/HCl pH 7.4; 100 mM of sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of factor XIa from Kordia (0.45 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 factor XIa substrate Boc-Glu(OBzl)-Ala-Arg-AMC dissolved in assay buffer (10 μM 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). The measured emissions of the test batches with test substance are compared to those of control batches without test substance (only dimethyl sulphoxide instead of test substance in dimethyl sulphoxide), and the IC50 values are calculated from the concentration/activity relationships.
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 501.87, ALogP 4.62, HBA 6, HBD 2, PSA 121.42, QED 0.49
Compound (SMILES): CC(C(=O)NC1COc2ncccc21)c1cccc(C(F)(F)F)c1Cl
InChIKey: CGZWZKJDTFHJQE-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: In Vitro Assay: Cell line generation was performed in general according to established molecular cloning protocols. Specifically, RNA was extracted from human whole blood using the Qiagen RNeasy kit (Qiagen, CH) according to the manufacturer's instructions. Subsequently cDNA was made (Superscript II, Invitrogen AG, CH) and the human P2X7 gene (genbank ref. BC011913) was amplified with the following primers: ATCGCGGCCGCTCAGTAAGGACTCTTGAAGCCACT and CGCCGCTAGCACCACCATGCCGGCCTGCTGCAGCTGCA. The amplified sequence was subsequently ligated into a pcDNA3.1 (+) NotI, NheI digested plasmid. Human embryonic kidney (HEK) cells (ATCC CRL-1573, Manassas, Va., USA) were transfected with the pcDNA3.1 (+). hP2X7 plasmid using lipofectamine 2000 (Invitrogen AG, CH) according to the manufacturer's instructions. Following a 24 h exposure to DNA, cells were trypsinized and re-seeded at low density in the presence of 250 ug Geneticin. Geneticin resistant cells were then selected during two consecutive rounds of cloning by serial limiting dilution with visual inspection.
Measurement: IC50 = 571 nM (pChEMBL 6.239999771118164)
Descriptors: MW 370.76, ALogP 4.11, HBA 3, HBD 1, PSA 51.22, QED 0.88
Compound (SMILES): CCOc1cc(N2CCC(CCS(C)(=O)=O)CC2)c(C)cc1Nc1nccc(-c2c(-c3ccc(OC(C)C)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: WDOTWXVYWDYVDJ-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 823.97, ALogP 8.88, HBA 11, HBD 2, PSA 140.05, QED 0.11
Compound (SMILES): CCOc1cc(N2CCN(C)CC2)ccc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: QHIGHCKBCQWHDJ-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 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 690.75, ALogP 6.89, HBA 10, HBD 2, PSA 109.15, QED 0.16
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1C1CCN(C(N)=O)CC1
InChIKey: VQODXNCHOGDXSX-YKSBVNFPSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Activity at human muscarinic acetylcholine receptor M1 transfected in CHO-K1 cells assessed as intracellular calcium levels in presence of acetylcholine by FLIPR assay
Measurement: Ki = 66.07 nM (pChEMBL 7.179999828338623)
Descriptors: MW 522.64, ALogP 4.45, HBA 6, HBD 1, PSA 80.28, QED 0.43
Compound (SMILES): COC(=O)c1cccnc1C#CCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: JBMDPQHNWRVKTP-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 534.58, ALogP 4.42, HBA 10, HBD 0, PSA 104.49, QED 0.22
Compound (SMILES): CC1CCN(C(=O)OC(C)(C)C)CC1c1nnn2cnc3[nH]ccc3c12
InChIKey: IVFATVRABARRFI-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 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 356.43, ALogP 2.97, HBA 6, HBD 1, PSA 88.41, QED 0.72
Compound (SMILES): COc1cc(OC)cc(N(CCNC(=O)C2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: ARDLUUQELBPNNT-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 472.55, ALogP 3.71, HBA 8, HBD 1, PSA 94.4, QED 0.4
Compound (SMILES): COc1cc(F)cc(C(=O)N2CCC(N3CC(CC#N)(n4cc(-c5ncnc6[nH]ccc56)cn4)C3)CC2)c1
InChIKey: IJRZRTMNZPOXPD-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 < 10 nM (pChEMBL 8)
Descriptors: MW 514.57, ALogP 3.2, HBA 8, HBD 1, PSA 115.96, QED 0.42
Compound (SMILES): CCS(=O)(=O)Nc1ccc(OCC(C)(C)C)c(-c2cn(C)c(=O)c3[nH]ccc23)c1
InChIKey: MAEDJUGOIKDPTL-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human N-terminal His6-tagged BRD4 BD1-BD2 (K57 to K550 residues) after 1 hr using alexa-647 conjugated probe by TR-FRET assay
Measurement: Ki = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 417.53, ALogP 3.72, HBA 5, HBD 2, PSA 93.19, QED 0.64
Compound (SMILES): COc1cc(C#N)ccc1N1CCOc2cc(S(=O)(=O)Nc3nccs3)ccc21
InChIKey: BCCZTFIOURKUIO-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human NaV1.5 expressed in HEK295 cells at holding potential of -125 mV with test potentials to -10 mV by whole cell voltage clamp method
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 428.5, ALogP 3.35, HBA 8, HBD 1, PSA 104.55, QED 0.66
Compound (SMILES): COCc1c(-c2cc3cc(C)cc(OC)c3s2)c2c(N)ncnn2c1CN1CCNC(=O)C1
InChIKey: HNLRRJSKGXOYNO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human recombinant FGFR2 in the presence of ATP at 0.8 uM measured after 1 hr by fluorescence based assay
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 466.57, ALogP 2.59, HBA 9, HBD 2, PSA 107.01, QED 0.45