lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(C)C(=O)c1ccc2c(c1)c(Oc1c(Cl)cccc1C(F)(F)F)nn2-c1ccc(C(=O)O)cc1
InChIKey: PRFOAGMHUSKCKE-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Activity at GAL4 DBD-fused LXRbeta LBD (unknown origin) expressed in human HG5LN cells after 18 hrs by luciferase reporter gene assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 503.86, ALogP 5.89, HBA 5, HBD 1, PSA 84.66, QED 0.37
Compound (SMILES): COc1ncccc1NC(=O)N1CCC(N2CC(CC#N)(n3cc(-c4ccnc5[nH]ccc45)cn3)C2)CC1
InChIKey: NDQXOJDSSACRIG-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 511.59, ALogP 3.45, HBA 8, HBD 2, PSA 127.99, QED 0.41
Compound (SMILES): COc1cc2c(Oc3ccc(NC(=O)c4cn(-c5ccccc5OC)cn4)cc3F)ccnc2cc1OCCCN1CCN(C)CC1
InChIKey: SJSWLZFLXRBNSJ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR-2 (unknown origin)
Measurement: IC50 = 589 nM (pChEMBL 6.230000019073486)
Descriptors: MW 640.72, ALogP 5.64, HBA 10, HBD 1, PSA 103.21, QED 0.17
Compound (SMILES): COCCS(=O)(=O)N[C@H]1CCc2c(-c3noc(-c4ccc(OC(C)C)c(C#N)c4)n3)cccc21
InChIKey: CCEAKDWEXPIAPE-NRFANRHFSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Agonist activity at human S1P5 expressed in bla TANGO U2OS cells assessed as inhibition of cAMP formation preincubated for 4 hrs followed by FRET-based beta-lactamase fluorescent substrate addition measured after 2 hrs
Measurement: EC50 = 173.55 nM (pChEMBL 6.760000228881836)
Descriptors: MW 482.56, ALogP 3.62, HBA 8, HBD 1, PSA 127.34, QED 0.49
Compound (SMILES): Cn1nccc1S(=O)(=O)N1CCC(N2CC(CC#N)(n3cc(-c4ncnc5[nH]ccc45)cn3)C2)CC1
InChIKey: UIZMYHBGWDBHMQ-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 506.6, ALogP 1.33, HBA 10, HBD 1, PSA 141.62, QED 0.41
Compound (SMILES): O=C(CC(F)(F)F)N1CCC(c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: HUYBEZVKAVEEFY-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 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 352.32, ALogP 2.26, HBA 5, HBD 1, PSA 79.18, QED 0.77
Compound (SMILES): COc1ccc(CNc2nc(N)c3nc(-c4ccco4)sc3n2)cc1
InChIKey: SRYURLBYUDXQGJ-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Inverse agonist activity at human adenosine A2A receptor expressed in CHO cells assessed as inhibition of cAMP accumulation measured after 150 mins in presence of [3H]cAMP by scintillation counting method
Measurement: IC50 = 187 nM (pChEMBL 6.730000019073486)
Descriptors: MW 353.41, ALogP 3.55, HBA 8, HBD 2, PSA 99.09, QED 0.57
Compound (SMILES): CC1(C)Cc2c(c(C(=O)Nc3ccc(C(F)(F)F)cc3)cc3nc(Nc4c(F)cccc4Cl)[nH]c23)O1
InChIKey: SMUHRFNGPGEYHA-UHFFFAOYSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O14684
Assay: Inhibition of human recombinant mPGES-1 expressed in CHO cells assessed as reduction in conversion of PGH2 to PGE2 incubated for 10 mins followed by substrate addition measured after 1 min in presence of GSH
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 518.9, ALogP 7.08, HBA 4, HBD 3, PSA 79.04, QED 0.25
Compound (SMILES): Cc1ccc(C#N)c(N2CCC(C(=O)N3CCC(N4CC(CC#N)(n5cc(-c6ncnc7[nH]ccc67)cn5)C4)CC3)CC2)n1
InChIKey: YJEJBPFDRLCYHJ-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 589.71, ALogP 3.23, HBA 10, HBD 1, PSA 146.65, QED 0.36
Compound (SMILES): CNCCn1cc(-c2cnc3ccc(N(CC4CC4)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: XOFNBYYGGHNBLH-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 = 7585.78 nM (pChEMBL 5.119999885559082)
Descriptors: MW 458.57, ALogP 4.28, HBA 8, HBD 1, PSA 77.33, QED 0.38
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCCC2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: PMWJNWXMNAKMHW-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 458.57, ALogP 4.66, HBA 7, HBD 1, PSA 79.4, QED 0.39
Compound (SMILES): Cn1c(=O)c2c(ccn2CC(=O)Nc2nc(-c3ccc(OC(F)(F)F)cc3)cs2)n(C)c1=O
InChIKey: MQBRPGZLHZUVDU-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 479.44, ALogP 2.7, HBA 9, HBD 1, PSA 100.15, QED 0.47
Compound (SMILES): COc1cc2c(Nc3cc(Cl)c(Cl)cc3F)ncnc2cc1OC[C@@H]1CO[C@H]2[C@@H]1OC[C@@H]2OC
InChIKey: KTBQYTJFMLOVMP-VNTFJFIFSA-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 510.35, ALogP 4.64, HBA 8, HBD 1, PSA 83.96, QED 0.46
Compound (SMILES): CCOc1cc(N2CCN(C)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: PGUQUVFEUSASNX-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 660.73, ALogP 6.88, HBA 9, HBD 2, PSA 99.92, QED 0.17
Compound (SMILES): NC(=O)C1(c2ccccc2CCc2nc(Nc3ccc(C4CCNCC4)nc3)ncc2C(F)(F)F)CC1
InChIKey: RTGQEFNYCLEWPU-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: VEGFR2: Adult human umbilical vein endothelial cells (HUVEC) (Cat# CC-2519, Lonza) were seeded into clear-bottom, TC treated 12 well plates (Cat #665180, Greiner Bio-One) in EGM-2 (Cat# CC-3162, Lonza) at 180,000 cells/well (volume 1 mL), and the plates incubated at 37° C. and 5% CO2 for 6 hours. The media was replaced with EBM-2 (Cat # CC-3156, Lonza)+0.1% BSA (Cat# A8412, Sigma) and cells incubated for a further period (overnight at 37° C. and 5% CO2).96 well Maxisorp immuno plates (Cat #439454, Nunc) were coated with 100 Î¼L of Total VEGFR2 capture antibody (Part #841434, Human Total VEGFR2/FLT4 ELISA Kit, Cat # DYC1780, R&D Systems), or Phospho VEGFR2 Capture antibody (Part #841419, Human Phospho VEGFR2/FLT4 ELISA Kit, Cat# DYC1766, R&D Systems). The plates were covered and incubated at room temperature overnight. The coating antibody was flicked out and the plates washed three times with Wash Buffer (Phosphate buffered saline (137 mM NaCl, 2.7 nM KCl, 8.1 nM Na2HPO4, 1.5 mL KH2PO4, pH 7.2-7.4), 0.05% Tween 20). 300 uL of blocking buffer (5% v/v Tween 20, 5% w/v sucrose in PBS) was then added to wells and plate incubated for 2 hours at room temperature.
Measurement: IC50 = 4083 nM (pChEMBL 5.389999866485596)
Descriptors: MW 510.56, ALogP 4.4, HBA 6, HBD 3, PSA 105.82, QED 0.41
Compound (SMILES): CCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: YPAFPGOEBJGULD-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 = 6309.57 nM (pChEMBL 5.199999809265137)
Descriptors: MW 389.46, ALogP 4.21, HBA 7, HBD 0, PSA 65.3, QED 0.49
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OC[C@H]1CN2CCC[C@H]2CO1
InChIKey: FSJDACURTSWGHC-JKSUJKDBSA-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 7.301000118255615)
Descriptors: MW 475.38, ALogP 4.93, HBA 7, HBD 1, PSA 68.74, QED 0.54
Compound (SMILES): Cc1cc(C(=O)N2CCC(N3CC(CC#N)(n4cc(-c5ncnc6[nH]ccc56)cn4)C3)CC2)c(C)o1
InChIKey: SMVCBLYKCXTELF-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 484.56, ALogP 3.26, HBA 8, HBD 1, PSA 119.87, QED 0.46
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4c(n3)-c3cc5c(F)cccc5n3CO4)cc12
InChIKey: GOHCXBUFLQKEIO-UHFFFAOYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of NS5B polymerase E1202G/T1280I/S2197P mutant in HCV genotype 1b infected in human HuH7 replicon cells after 72 hrs in presence of 10% FBS by luciferase-based reporter assay
Measurement: EC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 614.63, ALogP 6.17, HBA 7, HBD 1, PSA 106.67, QED 0.25
Compound (SMILES): CNC(=O)c1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCOC)c4)nc3c2)c1
InChIKey: VRFBGASVRUTQNG-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 486.58, ALogP 4.06, HBA 8, HBD 1, PSA 94.4, QED 0.36
Compound (SMILES): N#Cc1cnc2[nH]cc(C(=O)c3cccc(NS(=O)(=O)c4ccccc4)c3F)c2c1
InChIKey: RXTJGSUALHRESK-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin) using CEC as substrate after 15 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 420.43, ALogP 3.61, HBA 5, HBD 2, PSA 115.71, QED 0.48
Compound (SMILES): COc1ccc(F)cc1C(=O)N1CCC(N2CC(CC#N)(n3cc(-c4ncnc5[nH]ccc45)cn3)C2)CC1
InChIKey: KERVZMOHTHESEC-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 514.57, ALogP 3.2, HBA 8, HBD 1, PSA 115.96, QED 0.42
Compound (SMILES): OC[C@@]12C[C@@H]1[C@@H](n1cnc3c(N[C@@H](C4CCC4)C4CC4)nc(Cl)nc31)[C@H](O)[C@@H]2O
InChIKey: YLEQGEOHZFVIAR-OHTVDBCQSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3 H]2-[p-(2-carboxyethyl)phenyl-ethylamino]-5'-N-ethylcarboxamidoadenosine from recombinant human adenosine receptor A2A expressed in HEK293 cell membranes after 60 mins by liquid scintillation counting method
Measurement: Ki = 3940 nM (pChEMBL 5.409999847412109)
Descriptors: MW 419.91, ALogP 1.75, HBA 8, HBD 4, PSA 116.32, QED 0.53
Compound (SMILES): CC(O)CN1CCN(CC[S+]([O-])C(c2ccc(F)cc2)c2ccc(F)cc2)CC1
InChIKey: PHGOEMMHIGVMIN-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from human D4R expressed in HEK293 cell membranes incubated for 1 hr by radioligand binding assay
Measurement: Ki = 3820 nM (pChEMBL 5.420000076293945)
Descriptors: MW 422.54, ALogP 2.8, HBA 4, HBD 1, PSA 49.77, QED 0.67
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCCC(C(N)=O)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: VGCISMLLKUTUAO-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 515.62, ALogP 3.38, HBA 9, HBD 1, PSA 111.63, QED 0.36
Compound (SMILES): O=S(=O)(C1CCOCC1)N1CCN(c2ccc(OC[C@@H]3CO[C@@](Cn4ccnc4)(c4ccc(Cl)cc4Cl)O3)cc2)CC1
InChIKey: DVDVFRQEWILNEL-VAVYLYDRSA-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 = 226 nM (pChEMBL 6.650000095367432)
Descriptors: MW 637.59, ALogP 4.17, HBA 9, HBD 0, PSA 95.36, QED 0.35
Compound (SMILES): Cc1ccc(C2=C(C#N)C(=O)NC(c3ccc(OCCC(F)(F)F)cc3)(C(F)(F)F)C2)cc1
InChIKey: WBACZIGNMMQGOU-UHFFFAOYSA-N
Target: Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q10469
Assay: MGAT SPA Assay: MGAT2 enzyme was assayed using membranes isolated from Sf9 cells expressing the recombinant human MGAT2 cDNA with 2-monooleoylglycerol and [3H]-oleoyl-CoA as substrates as described by Seethala et al. [Anal. Biochem., 383(2):144-150 (Dec. 15, 2008)]. Briefly, the assays were conducted in 384-well plates in a total volume of 30 uL at 25° C. In each assay, 200 ng of recombinant human MGAT2 membrane was incubated with 10 uM of 2-monooleoylglycerol and 15 uM of [3H]-oleoyl-CoA in 100 mM potassium phosphate (pH 7.4) for 20 min with various concentrations of compounds delivered in DMSO. The assay was terminated by the addition of 20 ul of Stopping Solution (7.5 mg/ml Yttrium Oxide Polylysine beads, 3.3 mg/ml Fraction V BSA and 200 uM Mercuric chloride in 50 mM HEPES, pH 7.4). The signal was measured 1 h after quenching the reaction using LEADSEEKERSM for 5 minutes. To calculate the degree of inhibition, the zero level of enzyme activity (blank) was defined.
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 468.4, ALogP 5.58, HBA 3, HBD 1, PSA 62.12, QED 0.58
Compound (SMILES): COc1nn2cc(-c3cc4ccccc4o3)nc2s1
InChIKey: KNYUOTYXWJPDBX-UHFFFAOYSA-N
Target: Proteinase-activated receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI0
Assay: Antagonist activity at PAR4 in human platelet rich plasma assessed as inhibition of gamma-thrombin-induced platelet aggregation preincubated for 5 mins followed by gamma-thrombin addition and measured in presence of recombinant hirudin
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 271.3, ALogP 3.21, HBA 6, HBD 0, PSA 52.56, QED 0.56
Compound (SMILES): Cc1oc2c(c1CC(=O)Nc1nc(-c3ccc(OC(F)(F)F)c(Cl)c3)cs1)c(=O)n(C)c(=O)n2C
InChIKey: NLZYLJKBFOAYMA-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 528.9, ALogP 4, HBA 9, HBD 1, PSA 108.36, QED 0.42
Compound (SMILES): COc1ccccc1-c1cc(CN(C)C)ccc1Cl
InChIKey: GROYHNLGVCIQOI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Agonist activity at 5-HT7R (unknown origin) transfected in HEK293 cells expressing tTA-dependent luciferase reporter and beta arrestin 2-TEV fusion gene assessed as beta arrestin recruitment incubated for 22 hrs by Tango assay
Measurement: EC50 = 478.63 nM (pChEMBL 6.320000171661377)
Descriptors: MW 275.78, ALogP 4.08, HBA 2, HBD 0, PSA 12.47, QED 0.83
Compound (SMILES): CCS(=O)(=O)c1ccc(Cn2c(C)c(CC(=O)O)c3cccnc32)c(Cl)c1
InChIKey: ABSJDZWNXDCDKP-UHFFFAOYSA-N
Target: Prostaglandin D2 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y4
Assay: Displacement of [3H]-PGD2 from human CRTh2 expressed in CHO-K1 cell membranes incubated for 1 hr by SPA binding assay
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 406.89, ALogP 3.47, HBA 5, HBD 1, PSA 89.26, QED 0.68
Compound (SMILES): CC(C)c1nc(-c2nc3ccccc3[nH]2)c(N2CCN(C(=O)Cn3cnc4cccnc43)[C@H](C)C2)s1
InChIKey: BEMATWPFDYPDGS-QGZVFWFLSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells by Q patch-clamp method
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 500.63, ALogP 4.29, HBA 8, HBD 1, PSA 95.83, QED 0.39
Compound (SMILES): COc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4CO)nc3c2)c1
InChIKey: YURYMGHZHGYXAW-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 476.58, ALogP 3.68, HBA 9, HBD 2, PSA 97.56, QED 0.36
Compound (SMILES): CN(Cc1cccc(F)c1)S(=O)(=O)c1ccc2c(c1)C(=O)C(=O)N2
InChIKey: MORQEJVQYSEVCC-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAOB using kynuramine as substrate assessed as decrease in formation of 4-hydroxyquinoline incubated for 20 mins by fluorescence assay
Measurement: Ki = 3580 nM (pChEMBL 5.449999809265137)
Descriptors: MW 348.36, ALogP 1.78, HBA 4, HBD 1, PSA 83.55, QED 0.85
Compound (SMILES): COc1cc2c(Nc3ccc(Br)c(Cl)c3)ncnc2cc1O[C@H]1CO[C@@H]2CCO[C@H]12
InChIKey: JJQTYTQYXOULRB-UXPWSPDFSA-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 = 1000 nM (pChEMBL 6)
Descriptors: MW 492.76, ALogP 4.73, HBA 7, HBD 1, PSA 74.73, QED 0.55
Compound (SMILES): COc1cc(OC)cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)C(CNC(C)C)C(C)C)c1
InChIKey: YSROZQPVVLBKFI-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using Btn-Flt3 as substrate after 120 mins by TR-FRET assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 488.64, ALogP 5.21, HBA 8, HBD 1, PSA 77.33, QED 0.33
Compound (SMILES): CN(C)CCOc1ccc(/C(=C(/CCCO)c2ccccc2)c2ccc(O)cc2)cc1.Cl
InChIKey: FXEJPYMPHRIWOW-JTHROIFXSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Inverse agonist activity at ERRgamma (unknown origin) expressed in human AD293 cells after 24 hrs by beta-galactosidase/luciferase reporter gene assay
Measurement: IC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 417.55, ALogP 5.06, HBA 4, HBD 2, PSA 52.93, QED 0.45
Compound (SMILES): CC(C)[C@@H]1c2nn(-c3cccc(S(C)(=O)=O)c3)cc2CN1c1ncc(CO)c(C(F)(F)F)n1
InChIKey: NCZXBZJVJRJUSC-GOSISDBHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 3050 nM (pChEMBL 5.519999980926514)
Descriptors: MW 481.5, ALogP 3.29, HBA 8, HBD 1, PSA 101.21, QED 0.6
Compound (SMILES): O=C(OCC12CCN(CC1)CC2)c1c[nH]c2cc(OC(F)F)ccc12
InChIKey: GUKIAYZQCGKGEC-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
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 350.37, ALogP 3.41, HBA 4, HBD 1, PSA 54.56, QED 0.84
Compound (SMILES): CCOc1cc2ncnc(Nc3ccc4c(cnn4Cc4ccccc4)c3)c2cc1NC(=O)/C=C/CN(C)C
InChIKey: NWZQTNDYDHXMOE-DHZHZOJOSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Irreversible inhibition of human recombinant GST-tagged JAK3 expressed in baculovirus infected Sf9 insect cells assessed as reduction in polyglutamic acid-tyrosine phosphorylation after 30 mins by ELISA
Measurement: IC50 = 6880 nM (pChEMBL 5.159999847412109)
Descriptors: MW 521.63, ALogP 5.23, HBA 8, HBD 2, PSA 97.2, QED 0.24
Compound (SMILES): Cc1ccnc(-n2nnc3c2CCN(C(=O)c2cccc(C(F)(F)F)c2Cl)C3C)c1
InChIKey: YBKVGRQSYAWVKA-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Ca2+ flux assay: 1321N1 cells expressing the recombinant human or rat 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 μl 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 250× the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 μL of the compound into 300 μL of assay buffer. A further 3× dilution occurred when transferring 50 μL/well of the compound plate to 100 μL/well in the cell plate. Cells were incubated with test compounds and dye for 30 minutes. Calcium dye fluorescence was monitored in FLIPR as the cells were challenged by adding 50 μL/well of BzATP (final concentration is 250 μM BzATP (human and rat)). The fluorescence change was measured 180 seconds after adding the agonist. Peak fluorescence was plotted as a function of BzATP concentration using Origin 7 software.
Measurement: IC50 = 13.3 nM (pChEMBL 7.880000114440918)
Descriptors: MW 435.84, ALogP 4.4, HBA 5, HBD 0, PSA 63.91, QED 0.6
Compound (SMILES): CC(C)(N)C(=O)N1CC[C@](C)(N2CCc3c(-c4cnc(N)nc4)nc(N4CCOCC4)nc32)C1
InChIKey: NAPNAGZGKVCYGY-QHCPKHFHSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human PI3K p110delta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay
Measurement: Ki = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 467.58, ALogP 0.44, HBA 10, HBD 2, PSA 139.62, QED 0.65
Compound (SMILES): COc1cc(OC)c(C)c(N(CCO)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: RMVONVMXMXKGPN-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 419.49, ALogP 3.49, HBA 8, HBD 1, PSA 85.53, QED 0.49
Compound (SMILES): CC#CC(=O)N1CCC([C@@H]2CCNc3c(C(N)=O)c(-c4ccc(Oc5ccccc5)cc4)nn32)CC1
InChIKey: HJAUUHMYFPHMCT-QHCPKHFHSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK phosphorylation at Tyr 223 residue in human Ramos cell incubated for 3 hrs by HTRF-based analysis
Measurement: IC50 = 15.1 nM (pChEMBL 7.820000171661377)
Descriptors: MW 483.57, ALogP 4.06, HBA 6, HBD 2, PSA 102.48, QED 0.53
Compound (SMILES): CNCCN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(CC4CCOCC4)c3)nc2c1.Cl
InChIKey: ZFKDHRXSKPFOCM-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 502.62, ALogP 4.29, HBA 9, HBD 1, PSA 86.56, QED 0.34
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)Nc3nc4ccccc4s3)CC2)C1
InChIKey: SELBXFDJYLRDQM-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 538.64, ALogP 4.05, HBA 9, HBD 2, PSA 131.65, QED 0.35
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(SC)nc4)cc23)c1F
InChIKey: NPTDLIZHFMCABZ-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using MFC as substrate after 45 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 502.57, ALogP 5.01, HBA 6, HBD 2, PSA 104.81, QED 0.26
Compound (SMILES): Nc1nc(NCc2cccc(O)c2)nc2sc(-c3ccco3)nc12
InChIKey: CXAWOAYZDCLTRY-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Inverse agonist activity at human adenosine A2A receptor expressed in CHO cells assessed as inhibition of cAMP accumulation measured after 150 mins in presence of [3H]cAMP by scintillation counting method
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 339.38, ALogP 3.25, HBA 8, HBD 3, PSA 110.09, QED 0.52
Compound (SMILES): c1ccc(CN2CCN(c3cc(N4CCCC4)nc(N4CCCC4)n3)CC2)cc1
InChIKey: HSCFCMDPCFLHTC-UHFFFAOYSA-N
Target: Caspase-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P51878
Assay: Inhibition of human recombinant DTT-activated caspase-5 expressed in Escherichia coli using Ac-WEHD-AMC as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay
Measurement: Ki = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 392.55, ALogP 3, HBA 6, HBD 0, PSA 38.74, QED 0.78
Compound (SMILES): COC(=O)[C@H](CO)NC(=O)[C@H](CCCCNC1CC2CCC1C2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)c1ccccc1
InChIKey: KIVRLNZVHYCJSN-CEIAAXPSSA-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 834.03, ALogP 1.26, HBA 10, HBD 8, PSA 233.16, QED 0.06
Compound (SMILES): CN(C)CCOc1cccc(Nc2nccc(-c3c(-c4cccc(C(=O)Nc5ccc(F)cc5F)c4)nc4ccccn34)n2)c1
InChIKey: CBPHTJMAIXBGFS-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 605.65, ALogP 6.67, HBA 8, HBD 2, PSA 96.68, QED 0.18
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc(F)cc(C#N)c3)CC2)C1
InChIKey: WQNFTZOVCTXIKW-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 509.55, ALogP 3.06, HBA 8, HBD 1, PSA 130.52, QED 0.44
Compound (SMILES): Cc1oc2c(c1CC(=O)Nc1nc(-c3ccc(Cl)c(OC(F)(F)F)c3)cs1)c(=O)n(C)c(=O)n2C
InChIKey: GLTMCNDGYKDTAQ-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 528.9, ALogP 4, HBA 9, HBD 1, PSA 108.36, QED 0.42
Compound (SMILES): CC(C)[C@H](NS(=O)(=O)c1ccc(-c2cccc(CNC(=O)c3nc4ccccc4c(=O)[nH]3)c2)cc1)C(=O)NO
InChIKey: IWQSGINKBSWILJ-QHCPKHFHSA-N
Target: Matrix metalloproteinase-14 (SINGLE PROTEIN), Homo sapiens
UniProt: P50281
Assay: Inhibition of recombinant human GST-tagged MMP14 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 549.61, ALogP 2.33, HBA 7, HBD 5, PSA 170.35, QED 0.16
Compound (SMILES): CNCC(O)CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: LCWWFMHHNQAPDZ-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 448.53, ALogP 2.77, HBA 9, HBD 2, PSA 97.56, QED 0.4
Compound (SMILES): FC(F)(F)c1ccc(CN2CCC(c3[nH]c(=S)n4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: BKQDWCREZVQKTK-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 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 431.49, ALogP 5.27, HBA 4, HBD 2, PSA 52.12, QED 0.43
Compound (SMILES): N#CCC1(n2cc(-c3ccnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)Nc3ccc(F)cc3F)CC2)C1
InChIKey: CGJDVXSUNVYIDT-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 516.56, ALogP 4.33, HBA 6, HBD 2, PSA 105.87, QED 0.41
Compound (SMILES): OC1CCCCCCCNc2ncc3c(-c4cccnc4)cn(c3n2)CCCC1
InChIKey: XBFYWJOKBDZTSR-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 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 393.54, ALogP 4.79, HBA 6, HBD 2, PSA 75.86, QED 0.62
Compound (SMILES): CN1CCN(Cc2ccc(-c3cn4c5nc(ncc35)NCCCCCCCC(O)CCCC4)cc2)CC1
InChIKey: LZOJVTCTBSNNNT-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 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 504.72, ALogP 5.14, HBA 7, HBD 2, PSA 69.45, QED 0.51
Compound (SMILES): CCS(=O)(=O)c1ccc(Cn2c(C)c(CC(=O)O)c3cccnc32)c(C(F)(F)F)c1
InChIKey: GREROBNURFJIIN-UHFFFAOYSA-N
Target: Prostaglandin D2 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y4
Assay: Antagonist activity against human CRTh2 expressed in CHO-K1 cells assessed as inhibition of PGD2-mediated attenuation of forskolin-induced cAMP accumulation incubated for 60 mins by scintillation counting method
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 440.44, ALogP 3.83, HBA 5, HBD 1, PSA 89.26, QED 0.63
Compound (SMILES): COc1cc(N2CCN(CCS(C)(=O)=O)[C@@H](C(C)C)C2)ccc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: WSTUGSWTIWQVKH-UUWRZZSWSA-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 810.93, ALogP 6.94, HBA 12, HBD 2, PSA 143.29, QED 0.13
Compound (SMILES): C[C@]1(Nc2cnc(C(F)(F)F)cn2)CCC[C@@H]1NC(=O)c1ncccc1-n1nccn1
InChIKey: UNZFNWZMBMDMAR-UGSOOPFHSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Fluorescent Imaging Plate Reader (FLIPR) Assay: Orexin antagonist activity was determined by measuring changes in intracellular calcium levels using a Ca2+ sensitive fluorescent dye. The changes in fluorescent signal were monitored by Fluorescent Imaging Plate Reader (FLIPR®) technology available from Molecular Devices, LLC, U.S.A. Orexin mediated increases in intracellular Ca2+ concentration were readily detected upon activation with orexin-A. Twenty-four hours prior to the assay, RBL-2H3 cells stably expressing either human orexin receptor 1 or human orexin receptor 2 were seeded in cell culture medium in black, clear-bottom 384-well plates (commercially available from Corning Inc., U.S.A.) and grown overnight at 37 °C., 5% CO2. On the day of the assay, cell culture media was removed and cells were loaded with Calcium 5 Dye (commercially sold by Molecular Devices, LLC, U.S.A.) for 1 hour at 37 °C., 5% CO2.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 432.41, ALogP 2.62, HBA 8, HBD 2, PSA 110.51, QED 0.64
Compound (SMILES): COc1cc(OC)cc(N(CCN2[C@@H](C)CC[C@@H]2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: MLWCCXUMKLCBTL-PMACEKPBSA-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 486.62, ALogP 5.06, HBA 8, HBD 0, PSA 68.54, QED 0.34
Compound (SMILES): CCOc1ccc(Cc2ccc(CCC(=O)NO)cc2)cc1-c1nc2c(CC)nn(C)c2c(=O)[nH]1
InChIKey: OBSWAJPHUIIWSD-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length recombinant human N-terminal GST tagged HDAC6 expressed in baculovirus infected Sf9 cells using fluorogenic HDAC substrate after 30 mins by fluorescence analysis
Measurement: IC50 = 2350 nM (pChEMBL 5.630000114440918)
Descriptors: MW 475.55, ALogP 3.31, HBA 7, HBD 3, PSA 122.13, QED 0.25
Compound (SMILES): COc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4c(C)nn(C)c4C)nc3c2)c1.Cl
InChIKey: PVZCBJWZYVULRJ-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 474.61, ALogP 4.8, HBA 8, HBD 1, PSA 77.33, QED 0.37
Compound (SMILES): CC[C@@H](Nc1nc(Cl)nc2c1ncn2[C@H]1[C@H](O)[C@H](O)[C@]2(CO)C[C@H]12)C1CC1
InChIKey: UOHJOIXAJSMMCH-KJZWVPOSSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3 H]2-[p-(2-carboxyethyl)phenyl-ethylamino]-5'-N-ethylcarboxamidoadenosine from recombinant human adenosine receptor A2A expressed in HEK293 cell membranes after 60 mins by liquid scintillation counting method
Measurement: Ki = 1880 nM (pChEMBL 5.730000019073486)
Descriptors: MW 393.88, ALogP 1.36, HBA 8, HBD 4, PSA 116.32, QED 0.55
Compound (SMILES): N#CCC1(n2cc(-c3c(F)cnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3c(F)cncc3F)CC2)C1
InChIKey: CQHRLVINYXZBOO-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 520.52, ALogP 3.47, HBA 7, HBD 1, PSA 106.73, QED 0.43
Compound (SMILES): COc1cc(OC)cc(N(CC(=O)Nc2ncccc2OC)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: GSTHTWGRLIWKTQ-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 525.57, ALogP 4.23, HBA 10, HBD 1, PSA 116.52, QED 0.3
Compound (SMILES): O=C(Nc1ccccc1)Nc1ccc(C2CCNC2)cc1
InChIKey: FILGYOAPMPEHCJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Biochemical JAK and Tyk2 Kinase Assays: A panel of four LanthaScreen JAK biochemical assays (JAK1, 2, 3 and Tyk2) were carried in a common kinase reaction buffer (50 mM HEPES, pH 7.5, 0.01% Brij-35, 10 mM MgCl2, and 1 mM EGTA). Recombinant GST-tagged JAK enzymes and a GFP-tagged STAT1 peptide substrate were obtained from Life Technologies. Serially or discretely diluted compounds were pre-incubated with each of the four JAK enzymes and the substrate in white 384-well microplates (Corning) at ambient temperature for 1 h. ATP was subsequently added to initiate the kinase reactions in 10 μL total volume, with 1% DMSO. The final enzyme concentrations for JAK1, 2, 3 and Tyk2 are 4.2 nM, 0.1 nM, 1 nM, and 0.25 nM respectively; the corresponding Km ATP concentrations used are 25 μM, 3 μM, 1.6 μM, and 10 μM; while the substrate concentration is 200 nM for all four assays. Kinase reactions were allowed to proceed for 1 hour at ambient temperature before a 10 μL preparation of EDTA (10 mM final concentration) and Tb-anti-pSTAT1 (pTyr701) antibody (Life Technologies, 2 nM final concentration) in TR-FRET dilution buffer (Life Technologies) was added. The plates were allowed to incubate at ambient temperature for 1 h before being read on the EnVision reader (Perkin Elmer). Emission ratio signals (520 nm/495 nm) were recorded and utilized to calculate the percent inhibition values based on DMSO and background controls.For dose-response analysis, percent inhibition data were plotted vs. compound concentrations, and IC50 values were determined from a 4-parameter robust fit model with the Prism software (GraphPad Software). Results were expressed as pIC50 (negative logarithm of IC50) and subsequently converted to pKi (negative logarithm of dissociation constant, Ki) using the Cheng-Prusoff equation.
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 281.36, ALogP 3.41, HBA 2, HBD 3, PSA 53.16, QED 0.81
Compound (SMILES): Cc1cc(S(N)(=O)=O)ccc1Nc1ncc2c(n1)N(C)c1ccccc1C(=O)N2C
InChIKey: ACQZFXBAXXIVCX-UHFFFAOYSA-N
Target: Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma (SINGLE PROTEIN), Homo sapiens
UniProt: O75747
Assay: In Vitro Kinase Assay: The enzymatic activities against PI3K-α, PI3K-β, PI3K-γ and PI3K-δ were tested in ADAPTA assays. Activity against AURKB and AURKB were tested in Z′-Lyte assays. All assays were performed with ATP concentrations of Km for each kinase. BRD4_1 binding was tested using an AlphaScreen assay. All protocols are available from Life Technologies.
Measurement: IC50 = 822 nM (pChEMBL 6.079999923706055)
Descriptors: MW 424.49, ALogP 2.53, HBA 7, HBD 2, PSA 121.52, QED 0.66
Compound (SMILES): CSc1nc(N)cc(Oc2ccc(-c3nnc(Nc4cccc(C(F)(F)F)c4)[nH]3)cc2)n1
InChIKey: CMYHZFCJPORPHY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase-like 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92772
Assay: Competitive Binding Assay (KINOMEscan): For the competitive binding assay, test compounds were screened at 10 uM against 70 diverse kinase targets for competitive binding using the KINOMEscan technology (Ambit Biosciences) (Karaman, et al. (2008) Nature biotechnology 26:127-132). 11-point Kd curves were determined for hits identified during the initial screen.
Measurement: Kd = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 459.46, ALogP 5.12, HBA 8, HBD 3, PSA 114.63, QED 0.27