lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(F)c(-c2ccc3c(c2)C2(CCO3)N=C(C)C(N)=N2)c1
InChIKey: RSJMUFIUQMEIDV-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: TR-FRET Assay: The beta-secretase enzyme used in the TR-FRET is prepared as follows: The cDNA for the soluble part of the human beta-Secretase (AA 1-AA 460) was cloned using the ASP2-Fc10-1-IRES-GFP-neoK mammalian expression vector. The gene was fused to the Fc domain of IgG1 (affinity tag) and stably cloned into HEK 293 cells. Purified sBACE-Fc was stored in -80 C. in Tris buffer, pH 9.2 and had a purity of 40%.The enzyme (truncated form) was diluted to 6 ug/mL (stock 1.3 mg/mL) and the substrate (Europium)CEVNLDAEFK(Qsy7) to 200 nM (stock 120 uM) in reaction buffer (NaAcetate, chaps, triton x-100, EDTA pH4.5). The robotic systems Biomek FX and Velocity 11 were used for all liquid handling and the enzyme and substrate solutions were kept on ice until they were placed in the robotic system. Enzyme (9 ul) was added to the plate then 1 ul of compound in dimethylsulphoxide was added, mixed and pre-incubated for 10 minutes. Substrate (10 ul) was then added, mixed.
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 339.37, ALogP 3.27, HBA 5, HBD 1, PSA 69.2, QED 0.91
Compound (SMILES): [C-]#[N+]c1ccccc1-c1ccc(Cn2cccc(O)c2=S)cc1
InChIKey: KJRQWKHBCKSBAP-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Fluor de Lys Assay: Fluor de Lys is a fluorescence based HDAC activity assay comprising a combination of fluorogenic Histone deAcetylase Lysyl substrate and a developer. The kit is a highly sensitive and convenient alternative to radiolabeled, acetylated histones or peptide/HPLC methods for the assay of histone deacetylases. This assay is based on the ability of HeLa nuclear extract, which is enriched in HDAC activity, to mediate the deacetylation of the acetylated lysine side chain of the Fluor de Lys substrate. The assay procedure requires two steps. First, incubation of the HeLa nuclear extract with the Fluor de Lys substrate results in substrate deacetylation and thus sensitizes it to the second step. In the second step, treatment of the deacetylated substrate with the Fluor de Lys developer produces a fluorophore. The substrate-developer reaction, under normal circumstances goes to completion in less than 1 min at 25 C.
Measurement: IC50 = 372 nM (pChEMBL 6.429999828338623)
Descriptors: MW 318.4, ALogP 5.19, HBA 3, HBD 1, PSA 29.52, QED 0.53
Compound (SMILES): Oc1cccn(Cc2ccc(Cn3cc(-c4ccccc4)nn3)cc2)c1=S
InChIKey: APGDWCBKLVXBPR-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Fluor de Lys Assay: Fluor de Lys is a fluorescence based HDAC activity assay comprising a combination of fluorogenic Histone deAcetylase Lysyl substrate and a developer. The kit is a highly sensitive and convenient alternative to radiolabeled, acetylated histones or peptide/HPLC methods for the assay of histone deacetylases. This assay is based on the ability of HeLa nuclear extract, which is enriched in HDAC activity, to mediate the deacetylation of the acetylated lysine side chain of the Fluor de Lys substrate. The assay procedure requires two steps. First, incubation of the HeLa nuclear extract with the Fluor de Lys substrate results in substrate deacetylation and thus sensitizes it to the second step. In the second step, treatment of the deacetylated substrate with the Fluor de Lys developer produces a fluorophore. The substrate-developer reaction, under normal circumstances goes to completion in less than 1 min at 25 C.
Measurement: IC50 = 534 nM (pChEMBL 6.269999980926514)
Descriptors: MW 374.47, ALogP 4.28, HBA 6, HBD 1, PSA 55.87, QED 0.53
Compound (SMILES): COc1cc(F)c(-c2ccc(C(=O)O)cc2C)cc1-c1ccc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: CZRMENLRCXEIFA-GSBZAIBZSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay (SPA): First, low density lipoprotein (LDL) (Meridian) was biotinylated by incubating LDL with biotin for 1 hour on ice, after which it was dialyzed to remove free biotin. Then compounds at varying concentrations were incubated with 15 nM CETP (reagent production group, In Vitro Pharmacology, MRL Rahway) and 50 ug/ml of the biotinylated LDL in 50 mM HEPES, 150 mM NaCl, pH 7.4, for 1 hour at 37° C. The reaction was started by adding 3H-cholesterol ester high density lipoprotein (HDL) (American Radiochemicals Corp) at a concentration of ~0.6 nM. The reaction proceeded for 2 hours at 37° C., after which time it was quenched by the addition of 12% acetic acid. PVT streptavadin-coated scintillation proximity beads, which had been brought to room temperature, were then added at a concentration of 4 mg/ml. The assay was then mixed and counted after one half hour in a Microbeta plate reader.
Measurement: IC50 = 172 nM (pChEMBL 6.760000228881836)
Descriptors: MW 741.58, ALogP 10.63, HBA 4, HBD 1, PSA 76.07, QED 0.2
Compound (SMILES): COc1cc(F)c(C(C)C)cc1-c1ccc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: SQFSPEODJBYNSP-UNCTUWKVSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Inhibition of recombinant CETP (unknown origin) assessed as inhibition of transfer of [3H]cholesteryl oleate or [3H]triolein between exogenous [3H]LDL in 95% human serum by liquid scintillation analysis
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 595.56, ALogP 9.37, HBA 3, HBD 0, PSA 38.77, QED 0.28
Compound (SMILES): COc1cc(F)c(C(C)C)cc1-c1ccc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: IHQOEWDYVOETDQ-OHSXHVKISA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay (SPA): First, low density lipoprotein (LDL) (Meridian) was biotinylated by incubating LDL with biotin for 1 hour on ice, after which it was dialyzed to remove free biotin. Then compounds at varying concentrations were incubated with 15 nM CETP (reagent production group, In Vitro Pharmacology, MRL Rahway) and 50 ug/ml of the biotinylated LDL in 50 mM HEPES, 150 mM NaCl, pH 7.4, for 1 hour at 37° C. The reaction was started by adding 3H-cholesterol ester high density lipoprotein (HDL) (American Radiochemicals Corp) at a concentration of ~0.6 nM. The reaction proceeded for 2 hours at 37° C., after which time it was quenched by the addition of 12% acetic acid. PVT streptavadin-coated scintillation proximity beads, which had been brought to room temperature, were then added at a concentration of 4 mg/ml. The assay was then mixed and counted after one half hour in a Microbeta plate reader.
Measurement: IC50 = 261.5 nM (pChEMBL 6.579999923706055)
Descriptors: MW 599.52, ALogP 9.2, HBA 3, HBD 0, PSA 38.77, QED 0.27
Compound (SMILES): COc1cc(F)c(C(C)C)cc1-c1ccc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cccc(C(F)(F)F)c3)OC(=O)N12
InChIKey: QTTXWSVNQLUYMS-OHSXHVKISA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Inhibition of recombinant CETP (unknown origin) assessed as inhibition of transfer of [3H]cholesteryl oleate or [3H]triolein between exogenous [3H]LDL in 95% human serum by liquid scintillation analysis
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 581.53, ALogP 9.06, HBA 3, HBD 0, PSA 38.77, QED 0.28
Compound (SMILES): COc1cc(F)c(C(C)C)cc1-c1cnc(N(C)C)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: XTGSGBXFQNIZMO-PNIUZAESSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay (SPA): First, low density lipoprotein (LDL) (Meridian) was biotinylated by incubating LDL with biotin for 1 hour on ice, after which it was dialyzed to remove free biotin. Then compounds at varying concentrations were incubated with 15 nM CETP (reagent production group, In Vitro Pharmacology, MRL Rahway) and 50 ug/ml of the biotinylated LDL in 50 mM HEPES, 150 mM NaCl, pH 7.4, for 1 hour at 37° C. The reaction was started by adding 3H-cholesterol ester high density lipoprotein (HDL) (American Radiochemicals Corp) at a concentration of ~0.6 nM. The reaction proceeded for 2 hours at 37° C., after which time it was quenched by the addition of 12% acetic acid. PVT streptavadin-coated scintillation proximity beads, which had been brought to room temperature, were then added at a concentration of 4 mg/ml. The assay was then mixed and counted after one half hour in a Microbeta plate reader.
Measurement: IC50 = 69.73 nM (pChEMBL 7.159999847412109)
Descriptors: MW 625.59, ALogP 8.52, HBA 5, HBD 0, PSA 54.9, QED 0.26
Compound (SMILES): COc1ccc(-c2ccc(C(=O)O)cc2C)cc1-c1cnc(N(C)C)nc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: XDWVBQVFWMPRGF-FEVNIDIWSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay (SPA): First, low density lipoprotein (LDL) (Meridian) was biotinylated by incubating LDL with biotin for 1 hour on ice, after which it was dialyzed to remove free biotin. Then compounds at varying concentrations were incubated with 15 nM CETP (reagent production group, In Vitro Pharmacology, MRL Rahway) and 50 ug/ml of the biotinylated LDL in 50 mM HEPES, 150 mM NaCl, pH 7.4, for 1 hour at 37° C. The reaction was started by adding 3H-cholesterol ester high density lipoprotein (HDL) (American Radiochemicals Corp) at a concentration of ~0.6 nM. The reaction proceeded for 2 hours at 37° C., after which time it was quenched by the addition of 12% acetic acid. PVT streptavadin-coated scintillation proximity beads, which had been brought to room temperature, were then added at a concentration of 4 mg/ml. The assay was then mixed and counted after one half hour in a Microbeta plate reader.
Measurement: IC50 = 431.9 nM (pChEMBL 6.369999885559082)
Descriptors: MW 700.64, ALogP 8.33, HBA 7, HBD 1, PSA 105.09, QED 0.19
Compound (SMILES): COc1ccc(-c2ccc(C(=O)O)cc2C)cc1-c1cnc(N(C)C)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: KNWQVUVOSNPPMV-LYVYPOQBSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of Cav1.2 (unknown origin)
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 699.65, ALogP 8.93, HBA 6, HBD 1, PSA 92.2, QED 0.19
Compound (SMILES): COc1ccc([C@@H]2C[C@@H](O)[C@@H](O)C2)cc1-c1ccc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: KPSUBYGIYLFUSG-HBYAUOAXSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay (SPA): First, low density lipoprotein (LDL) (Meridian) was biotinylated by incubating LDL with biotin for 1 hour on ice, after which it was dialyzed to remove free biotin. Then compounds at varying concentrations were incubated with 15 nM CETP (reagent production group, In Vitro Pharmacology, MRL Rahway) and 50 ug/ml of the biotinylated LDL in 50 mM HEPES, 150 mM NaCl, pH 7.4, for 1 hour at 37° C. The reaction was started by adding 3H-cholesterol ester high density lipoprotein (HDL) (American Radiochemicals Corp) at a concentration of ~0.6 nM. The reaction proceeded for 2 hours at 37° C., after which time it was quenched by the addition of 12% acetic acid. PVT streptavadin-coated scintillation proximity beads, which had been brought to room temperature, were then added at a concentration of 4 mg/ml. The assay was then mixed and counted after one half hour in a Microbeta plate reader.
Measurement: IC50 = 418 nM (pChEMBL 6.380000114440918)
Descriptors: MW 689.57, ALogP 8.41, HBA 5, HBD 2, PSA 79.23, QED 0.26
Compound (SMILES): COc1cc(F)c(-c2ccc(C(=O)O)cc2C)cc1-c1cc(C)c(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: VWSXZBRQNVFYRD-LHHUKBANSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay (SPA): First, low density lipoprotein (LDL) (Meridian) was biotinylated by incubating LDL with biotin for 1 hour on ice, after which it was dialyzed to remove free biotin. Then compounds at varying concentrations were incubated with 15 nM CETP (reagent production group, In Vitro Pharmacology, MRL Rahway) and 50 ug/ml of the biotinylated LDL in 50 mM HEPES, 150 mM NaCl, pH 7.4, for 1 hour at 37° C. The reaction was started by adding 3H-cholesterol ester high density lipoprotein (HDL) (American Radiochemicals Corp) at a concentration of ~0.6 nM. The reaction proceeded for 2 hours at 37° C., after which time it was quenched by the addition of 12% acetic acid. PVT streptavadin-coated scintillation proximity beads, which had been brought to room temperature, were then added at a concentration of 4 mg/ml. The assay was then mixed and counted after one half hour in a Microbeta plate reader.
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 755.61, ALogP 10.94, HBA 4, HBD 1, PSA 76.07, QED 0.2
Compound (SMILES): COc1ccc(-c2ccc(C(=O)O)cc2C)cc1-c1c(C)cc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: WKTHTDSAZMPYTD-LYVYPOQBSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay (SPA): First, low density lipoprotein (LDL) (Meridian) was biotinylated by incubating LDL with biotin for 1 hour on ice, after which it was dialyzed to remove free biotin. Then compounds at varying concentrations were incubated with 15 nM CETP (reagent production group, In Vitro Pharmacology, MRL Rahway) and 50 ug/ml of the biotinylated LDL in 50 mM HEPES, 150 mM NaCl, pH 7.4, for 1 hour at 37° C. The reaction was started by adding 3H-cholesterol ester high density lipoprotein (HDL) (American Radiochemicals Corp) at a concentration of ~0.6 nM. The reaction proceeded for 2 hours at 37° C., after which time it was quenched by the addition of 12% acetic acid. PVT streptavadin-coated scintillation proximity beads, which had been brought to room temperature, were then added at a concentration of 4 mg/ml. The assay was then mixed and counted after one half hour in a Microbeta plate reader.
Measurement: IC50 = 87 nM (pChEMBL 7.059999942779541)
Descriptors: MW 737.62, ALogP 10.8, HBA 4, HBD 1, PSA 76.07, QED 0.2
Compound (SMILES): COc1ncc(-c2ccc(C(=O)O)cc2C)cc1-c1ccc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: ZOAPJFRUAASJIX-YTCPBCGMSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 674.57, ALogP 9, HBA 5, HBD 1, PSA 88.96, QED 0.21
Compound (SMILES): COc1ncc(-c2c(C)cc(C(=O)O)cc2C)cc1-c1ccc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: HGDZXEXIGIEYIU-TWLDFKIOSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Scintillation Proximity Assay (SPA): First, low density lipoprotein (LDL) (Meridian) was biotinylated by incubating LDL with biotin for 1 hour on ice, after which it was dialyzed to remove free biotin. Then compounds at varying concentrations were incubated with 15 nM CETP (reagent production group, In Vitro Pharmacology, MRL Rahway) and 50 ug/ml of the biotinylated LDL in 50 mM HEPES, 150 mM NaCl, pH 7.4, for 1 hour at 37° C. The reaction was started by adding 3H-cholesterol ester high density lipoprotein (HDL) (American Radiochemicals Corp) at a concentration of ~0.6 nM. The reaction proceeded for 2 hours at 37° C., after which time it was quenched by the addition of 12% acetic acid. PVT streptavadin-coated scintillation proximity beads, which had been brought to room temperature, were then added at a concentration of 4 mg/ml. The assay was then mixed and counted after one half hour in a Microbeta plate reader.
Measurement: IC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 688.6, ALogP 9.31, HBA 5, HBD 1, PSA 88.96, QED 0.2
Compound (SMILES): COc1ncc(-c2ccc(C(=O)O)cc2C)cc1-c1c(C)cc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: BQYWYJSLWHXISC-TWLDFKIOSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of Nav1.5 (unknown origin)
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 738.6, ALogP 10.19, HBA 5, HBD 1, PSA 88.96, QED 0.2
Compound (SMILES): COc1ccc(-c2c(C)cc(C(=O)O)cc2C)cc1-c1ncc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: KGTXNRGATFMNEY-NCZODNFJSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 738.6, ALogP 10.19, HBA 5, HBD 1, PSA 88.96, QED 0.2
Compound (SMILES): COc1ncc(-c2ccc(C(=O)O)cc2C)cc1-c1ncc(C(F)(F)F)cc1[C@@H]1CC[C@H]2[C@@H](c3cc(C(F)(F)F)cc(C(F)(F)F)c3)OC(=O)N12
InChIKey: SVVFIIYREHMBTN-UNCTUWKVSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of Cav1.2 (unknown origin)
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 725.56, ALogP 9.28, HBA 6, HBD 1, PSA 101.85, QED 0.2
Compound (SMILES): CC(=O)c1cn(C)c2ccc(Nc3nccc(-n4cc(CN5CC(O)C5)c(C)n4)n3)cc12
InChIKey: LVDAOOBTKGLDAK-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Inhibition Assay: Compounds of the invention were initially diluted to 10 mM in 100% DMSO (CALBIOCHEM) for storage and made into kinase buffer solution to create a compound concentration ranging from 1 uM and 10 uM. Serial dilutions of compounds of the invention were dispensed into a 96-well plate (GREINER BIOSCIENCES) at 6 uL each. Purified full-length human SYK, and KDR (CARNA BIOSCIENCES) were diluted in kinase buffer and added to the compound solutions and pre-incubated for 30 minutes at room temperature. Next, ATP (TEKNOVA) of Km (15 uM) and substrate solution (suggested manufacture substrates of PerkinElmer, for example, Ulight-TK peptide for SYK and Ulight-JAK1 for KDR (PERKINELMER)) was added (12 uL each) to the wells containing the compound solution and enzyme. The reaction mixture was incubated for 1 hour. Following the incubation, the stop solution made with EDTA, water, and Lance detection buffer (PERKINELMER) was added (12 uL each) to stop phosphorylation.
Measurement: IC50 = 345.6 nM (pChEMBL 6.460000038146973)
Descriptors: MW 431.5, ALogP 2.59, HBA 9, HBD 2, PSA 101.1, QED 0.45
Compound (SMILES): Cc1nn(-c2ccnc(Nc3ccc4c(c3)c(Cl)nn4C(C)C)n2)cc1CN1CC(O)C1
InChIKey: UVFZHIQEWCFGHT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Kinase Inhibition Assay: Compounds of the invention were initially diluted to 10 mM in 100% DMSO (CALBIOCHEM) for storage and made into kinase buffer solution to create a compound concentration ranging from 1 uM and 10 uM. Serial dilutions of compounds of the invention were dispensed into a 96-well plate (GREINER BIOSCIENCES) at 6 uL each. Purified full-length human SYK, and KDR (CARNA BIOSCIENCES) were diluted in kinase buffer and added to the compound solutions and pre-incubated for 30 minutes at room temperature. Next, ATP (TEKNOVA) of Km (15 uM) and substrate solution (suggested manufacture substrates of PerkinElmer, for example, Ulight-TK peptide for SYK and Ulight-JAK1 for KDR (PERKINELMER)) was added (12 uL each) to the wells containing the compound solution and enzyme. The reaction mixture was incubated for 1 hour. Following the incubation, the stop solution made with EDTA, water, and Lance detection buffer (PERKINELMER) was added (12 uL each) to stop phosphorylation.
Measurement: IC50 = 12.6 nM (pChEMBL 7.900000095367432)
Descriptors: MW 452.95, ALogP 3.47, HBA 9, HBD 2, PSA 96.92, QED 0.46
Compound (SMILES): Cc1nn(-c2ccnc(Nc3ccc4oc(C)c(Cl)c4c3)n2)cc1CN1CC(O)C1
InChIKey: WBUNQKQCIRJAJW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Kinase Inhibition Assay: Compounds of the invention were initially diluted to 10 mM in 100% DMSO (CALBIOCHEM) for storage and made into kinase buffer solution to create a compound concentration ranging from 1 uM and 10 uM. Serial dilutions of compounds of the invention were dispensed into a 96-well plate (GREINER BIOSCIENCES) at 6 uL each. Purified full-length human SYK, and KDR (CARNA BIOSCIENCES) were diluted in kinase buffer and added to the compound solutions and pre-incubated for 30 minutes at room temperature. Next, ATP (TEKNOVA) of Km (15 uM) and substrate solution (suggested manufacture substrates of PerkinElmer, for example, Ulight-TK peptide for SYK and Ulight-JAK1 for KDR (PERKINELMER)) was added (12 uL each) to the wells containing the compound solution and enzyme. The reaction mixture was incubated for 1 hour. Following the incubation, the stop solution made with EDTA, water, and Lance detection buffer (PERKINELMER) was added (12 uL each) to stop phosphorylation.
Measurement: IC50 = 24.3 nM (pChEMBL 7.610000133514404)
Descriptors: MW 424.89, ALogP 3.6, HBA 8, HBD 2, PSA 92.24, QED 0.51
Compound (SMILES): Cc1nn(-c2nc(Nc3ccc4c(c3)c(Cl)c(C)n4C)ncc2F)cc1CN1CC(O)C1
InChIKey: SJOQLVNIVBIOCX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Kinase Inhibition Assay: Compounds of the invention were initially diluted to 10 mM in 100% DMSO (CALBIOCHEM) for storage and made into kinase buffer solution to create a compound concentration ranging from 1 uM and 10 uM. Serial dilutions of compounds of the invention were dispensed into a 96-well plate (GREINER BIOSCIENCES) at 6 uL each. Purified full-length human SYK, and KDR (CARNA BIOSCIENCES) were diluted in kinase buffer and added to the compound solutions and pre-incubated for 30 minutes at room temperature. Next, ATP (TEKNOVA) of Km (15 uM) and substrate solution (suggested manufacture substrates of PerkinElmer, for example, Ulight-TK peptide for SYK and Ulight-JAK1 for KDR (PERKINELMER)) was added (12 uL each) to the wells containing the compound solution and enzyme. The reaction mixture was incubated for 1 hour. Following the incubation, the stop solution made with EDTA, water, and Lance detection buffer (PERKINELMER) was added (12 uL each) to stop phosphorylation.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 455.93, ALogP 3.48, HBA 8, HBD 2, PSA 84.03, QED 0.48
Compound (SMILES): Cc1nn(-c2ccnc(Nc3ccc4c(c3)c(-c3nccs3)cn4C)n2)cc1CN1CC(O)C1
InChIKey: MJVGTLKDJSROLS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Kinase Inhibition Assay: Compounds of the invention were initially diluted to 10 mM in 100% DMSO (CALBIOCHEM) for storage and made into kinase buffer solution to create a compound concentration ranging from 1 uM and 10 uM. Serial dilutions of compounds of the invention were dispensed into a 96-well plate (GREINER BIOSCIENCES) at 6 uL each. Purified full-length human SYK, and KDR (CARNA BIOSCIENCES) were diluted in kinase buffer and added to the compound solutions and pre-incubated for 30 minutes at room temperature. Next, ATP (TEKNOVA) of Km (15 uM) and substrate solution (suggested manufacture substrates of PerkinElmer, for example, Ulight-TK peptide for SYK and Ulight-JAK1 for KDR (PERKINELMER)) was added (12 uL each) to the wells containing the compound solution and enzyme. The reaction mixture was incubated for 1 hour. Following the incubation, the stop solution made with EDTA, water, and Lance detection buffer (PERKINELMER) was added (12 uL each) to stop phosphorylation.
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 472.58, ALogP 3.51, HBA 10, HBD 2, PSA 96.92, QED 0.39
Compound (SMILES): Cc1cn(-c2nc(Nc3ccc4c(c3)c(Cl)nn4C)ncc2F)cc1CN1CC(O)C1
InChIKey: TVTNEIYFFRQSMV-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Inhibition Assay: Compounds of the invention were initially diluted to 10 mM in 100% DMSO (CALBIOCHEM) for storage and made into kinase buffer solution to create a compound concentration ranging from 1 uM and 10 uM. Serial dilutions of compounds of the invention were dispensed into a 96-well plate (GREINER BIOSCIENCES) at 6 uL each. Purified full-length human SYK, and KDR (CARNA BIOSCIENCES) were diluted in kinase buffer and added to the compound solutions and pre-incubated for 30 minutes at room temperature. Next, ATP (TEKNOVA) of Km (15 uM) and substrate solution (suggested manufacture substrates of PerkinElmer, for example, Ulight-TK peptide for SYK and Ulight-JAK1 for KDR (PERKINELMER)) was added (12 uL each) to the wells containing the compound solution and enzyme. The reaction mixture was incubated for 1 hour. Following the incubation, the stop solution made with EDTA, water, and Lance detection buffer (PERKINELMER) was added (12 uL each) to stop phosphorylation.
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 441.9, ALogP 3.18, HBA 8, HBD 2, PSA 84.03, QED 0.49
Compound (SMILES): Cc1nn(-c2ccnc(Nc3ccc4c(c3)c(C(=O)C3CC3)cn4C)n2)cc1CN1CC[C@@H](O)C1
InChIKey: FNGJTJGYKVSXHA-HXUWFJFHSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Kinase Inhibition Assay: Compounds of the invention were initially diluted to 10 mM in 100% DMSO (CALBIOCHEM) for storage and made into kinase buffer solution to create a compound concentration ranging from 1 uM and 10 uM. Serial dilutions of compounds of the invention were dispensed into a 96-well plate (GREINER BIOSCIENCES) at 6 uL each. Purified full-length human SYK, and KDR (CARNA BIOSCIENCES) were diluted in kinase buffer and added to the compound solutions and pre-incubated for 30 minutes at room temperature. Next, ATP (TEKNOVA) of Km (15 uM) and substrate solution (suggested manufacture substrates of PerkinElmer, for example, Ulight-TK peptide for SYK and Ulight-JAK1 for KDR (PERKINELMER)) was added (12 uL each) to the wells containing the compound solution and enzyme. The reaction mixture was incubated for 1 hour. Following the incubation, the stop solution made with EDTA, water, and Lance detection buffer (PERKINELMER) was added (12 uL each) to stop phosphorylation.
Measurement: IC50 = 0.1 nM (pChEMBL 10)
Descriptors: MW 471.57, ALogP 3.37, HBA 9, HBD 2, PSA 101.1, QED 0.4
Compound (SMILES): Cc1nn(-c2cccc(Nc3ccc4c(c3)c(C(=O)C(F)(F)F)cn4C)n2)cc1CN1CC[C@@H](O)C1
InChIKey: QIYGHNDMIXXLHX-GOSISDBHSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Kinase Inhibition Assay: Compounds of the invention were initially diluted to 10 mM in 100% DMSO (CALBIOCHEM) for storage and made into kinase buffer solution to create a compound concentration ranging from 1 uM and 10 uM. Serial dilutions of compounds of the invention were dispensed into a 96-well plate (GREINER BIOSCIENCES) at 6 uL each. Purified full-length human SYK, and KDR (CARNA BIOSCIENCES) were diluted in kinase buffer and added to the compound solutions and pre-incubated for 30 minutes at room temperature. Next, ATP (TEKNOVA) of Km (15 uM) and substrate solution (suggested manufacture substrates of PerkinElmer, for example, Ulight-TK peptide for SYK and Ulight-JAK1 for KDR (PERKINELMER)) was added (12 uL each) to the wells containing the compound solution and enzyme. The reaction mixture was incubated for 1 hour. Following the incubation, the stop solution made with EDTA, water, and Lance detection buffer (PERKINELMER) was added (12 uL each) to stop phosphorylation.
Measurement: IC50 = 0.1 nM (pChEMBL 10)
Descriptors: MW 498.51, ALogP 4.12, HBA 8, HBD 2, PSA 88.21, QED 0.39
Compound (SMILES): CC(=O)c1c[nH]c2ccc(Nc3nccc(-n4cc(CN5CC(O)C5)c(C)n4)n3)cc12
InChIKey: JHXAYGBXXCDEBZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Kinase Inhibition Assay: Compounds of the invention were initially diluted to 10 mM in 100% DMSO (CALBIOCHEM) for storage and made into kinase buffer solution to create a compound concentration ranging from 1 uM and 10 uM. Serial dilutions of compounds of the invention were dispensed into a 96-well plate (GREINER BIOSCIENCES) at 6 uL each. Purified full-length human SYK, and KDR (CARNA BIOSCIENCES) were diluted in kinase buffer and added to the compound solutions and pre-incubated for 30 minutes at room temperature. Next, ATP (TEKNOVA) of Km (15 uM) and substrate solution (suggested manufacture substrates of PerkinElmer, for example, Ulight-TK peptide for SYK and Ulight-JAK1 for KDR (PERKINELMER)) was added (12 uL each) to the wells containing the compound solution and enzyme. The reaction mixture was incubated for 1 hour. Following the incubation, the stop solution made with EDTA, water, and Lance detection buffer (PERKINELMER) was added (12 uL each) to stop phosphorylation.
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 417.47, ALogP 2.57, HBA 8, HBD 3, PSA 111.96, QED 0.41
Compound (SMILES): Cc1nn(-c2ccnc(Nc3ccc4c(c3)c(Cl)c(C)n4C)n2)cc1CN1C[C@H](O)C[C@H]1C(=O)O
InChIKey: HKQWRPBPKJYWBK-XLIONFOSSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Inhibition Assay: Compounds of the invention were initially diluted to 10 mM in 100% DMSO (CALBIOCHEM) for storage and made into kinase buffer solution to create a compound concentration ranging from 1 uM and 10 uM. Serial dilutions of compounds of the invention were dispensed into a 96-well plate (GREINER BIOSCIENCES) at 6 uL each. Purified full-length human SYK, and KDR (CARNA BIOSCIENCES) were diluted in kinase buffer and added to the compound solutions and pre-incubated for 30 minutes at room temperature. Next, ATP (TEKNOVA) of Km (15 uM) and substrate solution (suggested manufacture substrates of PerkinElmer, for example, Ulight-TK peptide for SYK and Ulight-JAK1 for KDR (PERKINELMER)) was added (12 uL each) to the wells containing the compound solution and enzyme. The reaction mixture was incubated for 1 hour. Following the incubation, the stop solution made with EDTA, water, and Lance detection buffer (PERKINELMER) was added (12 uL each) to stop phosphorylation.
Measurement: IC50 = 9458 nM (pChEMBL 5.019999980926514)
Descriptors: MW 495.97, ALogP 3.19, HBA 9, HBD 3, PSA 121.33, QED 0.37
Compound (SMILES): COC[C@@H]1C[C@@H](O)CN1Cc1cn(-c2ccnc(Nc3ccc4c(c3)c(Cl)c(C)n4C)n2)nc1C
InChIKey: HJHMQIMVSSZTML-VQTJNVASSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Inhibition Assay: Compounds of the invention were initially diluted to 10 mM in 100% DMSO (CALBIOCHEM) for storage and made into kinase buffer solution to create a compound concentration ranging from 1 uM and 10 uM. Serial dilutions of compounds of the invention were dispensed into a 96-well plate (GREINER BIOSCIENCES) at 6 uL each. Purified full-length human SYK, and KDR (CARNA BIOSCIENCES) were diluted in kinase buffer and added to the compound solutions and pre-incubated for 30 minutes at room temperature. Next, ATP (TEKNOVA) of Km (15 uM) and substrate solution (suggested manufacture substrates of PerkinElmer, for example, Ulight-TK peptide for SYK and Ulight-JAK1 for KDR (PERKINELMER)) was added (12 uL each) to the wells containing the compound solution and enzyme. The reaction mixture was incubated for 1 hour. Following the incubation, the stop solution made with EDTA, water, and Lance detection buffer (PERKINELMER) was added (12 uL each) to stop phosphorylation.
Measurement: IC50 = 8372 nM (pChEMBL 5.079999923706055)
Descriptors: MW 496.02, ALogP 3.75, HBA 9, HBD 2, PSA 93.26, QED 0.4
Compound (SMILES): Cc1nn(-c2ccnc(Nc3ccc4c(c3)c(Cl)c(C)n4C)n2)cc1CCN1CC[C@@H](O)C1
InChIKey: DNYADMLAYDQAON-LJQANCHMSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Inhibition Assay: Compounds of the invention were initially diluted to 10 mM in 100% DMSO (CALBIOCHEM) for storage and made into kinase buffer solution to create a compound concentration ranging from 1 uM and 10 uM. Serial dilutions of compounds of the invention were dispensed into a 96-well plate (GREINER BIOSCIENCES) at 6 uL each. Purified full-length human SYK, and KDR (CARNA BIOSCIENCES) were diluted in kinase buffer and added to the compound solutions and pre-incubated for 30 minutes at room temperature. Next, ATP (TEKNOVA) of Km (15 uM) and substrate solution (suggested manufacture substrates of PerkinElmer, for example, Ulight-TK peptide for SYK and Ulight-JAK1 for KDR (PERKINELMER)) was added (12 uL each) to the wells containing the compound solution and enzyme. The reaction mixture was incubated for 1 hour. Following the incubation, the stop solution made with EDTA, water, and Lance detection buffer (PERKINELMER) was added (12 uL each) to stop phosphorylation.
Measurement: IC50 = 2109 nM (pChEMBL 5.679999828338623)
Descriptors: MW 465.99, ALogP 3.78, HBA 8, HBD 2, PSA 84.03, QED 0.45
Compound (SMILES): CO[C@@H]1CN(Cc2cn(-c3ccnc(Nc4ccc5c(c4)c(Cl)c(C)n5C)n3)nc2C)C[C@@H]1O
InChIKey: SRTUGXIMQMBQQX-LEWJYISDSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Inhibition Assay: Compounds of the invention were initially diluted to 10 mM in 100% DMSO (CALBIOCHEM) for storage and made into kinase buffer solution to create a compound concentration ranging from 1 uM and 10 uM. Serial dilutions of compounds of the invention were dispensed into a 96-well plate (GREINER BIOSCIENCES) at 6 uL each. Purified full-length human SYK, and KDR (CARNA BIOSCIENCES) were diluted in kinase buffer and added to the compound solutions and pre-incubated for 30 minutes at room temperature. Next, ATP (TEKNOVA) of Km (15 uM) and substrate solution (suggested manufacture substrates of PerkinElmer, for example, Ulight-TK peptide for SYK and Ulight-JAK1 for KDR (PERKINELMER)) was added (12 uL each) to the wells containing the compound solution and enzyme. The reaction mixture was incubated for 1 hour. Following the incubation, the stop solution made with EDTA, water, and Lance detection buffer (PERKINELMER) was added (12 uL each) to stop phosphorylation.
Measurement: IC50 = 731 nM (pChEMBL 6.139999866485596)
Descriptors: MW 481.99, ALogP 3.36, HBA 9, HBD 2, PSA 93.26, QED 0.44
Compound (SMILES): Cc1nn(-c2ccnc(Nc3ccc4c(c3)c(Cl)c(C)n4C)n2)cc1CN1C[C@H](O)C[C@H]1C
InChIKey: GCGAGXWTXGPHLP-AUUYWEPGSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Kinase Inhibition Assay: Compounds of the invention were initially diluted to 10 mM in 100% DMSO (CALBIOCHEM) for storage and made into kinase buffer solution to create a compound concentration ranging from 1 uM and 10 uM. Serial dilutions of compounds of the invention were dispensed into a 96-well plate (GREINER BIOSCIENCES) at 6 uL each. Purified full-length human SYK, and KDR (CARNA BIOSCIENCES) were diluted in kinase buffer and added to the compound solutions and pre-incubated for 30 minutes at room temperature. Next, ATP (TEKNOVA) of Km (15 uM) and substrate solution (suggested manufacture substrates of PerkinElmer, for example, Ulight-TK peptide for SYK and Ulight-JAK1 for KDR (PERKINELMER)) was added (12 uL each) to the wells containing the compound solution and enzyme. The reaction mixture was incubated for 1 hour. Following the incubation, the stop solution made with EDTA, water, and Lance detection buffer (PERKINELMER) was added (12 uL each) to stop phosphorylation.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 465.99, ALogP 4.12, HBA 8, HBD 2, PSA 84.03, QED 0.46
Compound (SMILES): Cc1nn(-c2ccnc(Nc3ccc4c(c3)c(S(C)(=O)=O)nn4C)n2)cc1CN1C[C@@H](O)[C@@H](O)C1
InChIKey: HXCYFHWOPRZEBU-KDURUIRLSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Inhibition Assay: Compounds of the invention were initially diluted to 10 mM in 100% DMSO (CALBIOCHEM) for storage and made into kinase buffer solution to create a compound concentration ranging from 1 uM and 10 uM. Serial dilutions of compounds of the invention were dispensed into a 96-well plate (GREINER BIOSCIENCES) at 6 uL each. Purified full-length human SYK, and KDR (CARNA BIOSCIENCES) were diluted in kinase buffer and added to the compound solutions and pre-incubated for 30 minutes at room temperature. Next, ATP (TEKNOVA) of Km (15 uM) and substrate solution (suggested manufacture substrates of PerkinElmer, for example, Ulight-TK peptide for SYK and Ulight-JAK1 for KDR (PERKINELMER)) was added (12 uL each) to the wells containing the compound solution and enzyme. The reaction mixture was incubated for 1 hour. Following the incubation, the stop solution made with EDTA, water, and Lance detection buffer (PERKINELMER) was added (12 uL each) to stop phosphorylation.
Measurement: IC50 = 647 nM (pChEMBL 6.190000057220459)
Descriptors: MW 498.57, ALogP 0.54, HBA 12, HBD 3, PSA 151.29, QED 0.34
Compound (SMILES): CCCn1c(C)c(Cl)c2cc(Nc3nccc(-n4cc(CN5CC(O)C5)c(C)n4)n3)ccc21
InChIKey: SDBGQUQLHJSYJN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Kinase Inhibition Assay: Compounds of the invention were initially diluted to 10 mM in 100% DMSO (CALBIOCHEM) for storage and made into kinase buffer solution to create a compound concentration ranging from 1 uM and 10 uM. Serial dilutions of compounds of the invention were dispensed into a 96-well plate (GREINER BIOSCIENCES) at 6 uL each. Purified full-length human SYK, and KDR (CARNA BIOSCIENCES) were diluted in kinase buffer and added to the compound solutions and pre-incubated for 30 minutes at room temperature. Next, ATP (TEKNOVA) of Km (15 uM) and substrate solution (suggested manufacture substrates of PerkinElmer, for example, Ulight-TK peptide for SYK and Ulight-JAK1 for KDR (PERKINELMER)) was added (12 uL each) to the wells containing the compound solution and enzyme. The reaction mixture was incubated for 1 hour. Following the incubation, the stop solution made with EDTA, water, and Lance detection buffer (PERKINELMER) was added (12 uL each) to stop phosphorylation.
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 465.99, ALogP 4.22, HBA 8, HBD 2, PSA 84.03, QED 0.42
Compound (SMILES): O=C(NCc1nnc2n1CCC2)c1cnc(Oc2ccc3c(c2)CCC(c2ccccc2)O3)s1
InChIKey: FMETUUJKGDCDMN-UHFFFAOYSA-N
Target: Sodium/calcium exchanger 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32418
Assay: Forward Mode Assay: The assay is based on the monitoring of intracellular Ca2+concentrations using the PBX Calcium Assay Kit from BD (Becton, Dickinson and Company) with calcium indicator dye 51-9000177BKa (BD, 640177), CHO cells expressing NCX1 were loaded with the dye, and after a preincubation period with the test compound, lonomycin (Calbiochem, 407950) was added. Ionomycin is an ionophor for Ca2+ions mediating an increase of intracellular Ca2+ions. Consequently, intracellular Ca2+ions are exchanged against extracellular Na+ions (Ca2+efflux, forward mode). The decrease of intracellular Ca2+ions was detected by measuring the fluorescence of the calcium indicator dye at a wavelength of 520 nm by a FLIPR device.Briefly, similarly as for the reverse mode, for the forward mode transport assay 18000 cells per well were seeded into a 96 well microplate (Corning COSTAR 3904) and incubated overnight in culture medium (cf. above). A total volume of 100 ul medium per well was used.
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 473.56, ALogP 4.47, HBA 8, HBD 1, PSA 91.16, QED 0.44
Compound (SMILES): CC(NC(=O)c1cnc(Oc2ccc3c(c2)CCC(c2cccc(F)c2)O3)s1)c1ccncc1
InChIKey: SOBIFKNKVWFAHD-UHFFFAOYSA-N
Target: Sodium/calcium exchanger 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32418
Assay: Forward Mode Assay: The assay is based on the monitoring of intracellular Ca2+concentrations using the PBX Calcium Assay Kit from BD (Becton, Dickinson and Company) with calcium indicator dye 51-9000177BKa (BD, 640177), CHO cells expressing NCX1 were loaded with the dye, and after a preincubation period with the test compound, lonomycin (Calbiochem, 407950) was added. Ionomycin is an ionophor for Ca2+ions mediating an increase of intracellular Ca2+ions. Consequently, intracellular Ca2+ions are exchanged against extracellular Na+ions (Ca2+efflux, forward mode). The decrease of intracellular Ca2+ions was detected by measuring the fluorescence of the calcium indicator dye at a wavelength of 520 nm by a FLIPR device.Briefly, similarly as for the reverse mode, for the forward mode transport assay 18000 cells per well were seeded into a 96 well microplate (Corning COSTAR 3904) and incubated overnight in culture medium (cf. above). A total volume of 100 ul medium per well was used.
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 475.55, ALogP 6.03, HBA 6, HBD 1, PSA 73.34, QED 0.37
Compound (SMILES): Cc1c(CNC(=O)c2cnc(Oc3ccc4c(c3)CCC(c3ccccc3)O4)s2)cnn1C
InChIKey: SZXRJWBLACXTIR-UHFFFAOYSA-N
Target: Sodium/calcium exchanger 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32418
Assay: Forward Mode Assay: The assay is based on the monitoring of intracellular Ca2+concentrations using the PBX Calcium Assay Kit from BD (Becton, Dickinson and Company) with calcium indicator dye 51-9000177BKa (BD, 640177), CHO cells expressing NCX1 were loaded with the dye, and after a preincubation period with the test compound, lonomycin (Calbiochem, 407950) was added. Ionomycin is an ionophor for Ca2+ions mediating an increase of intracellular Ca2+ions. Consequently, intracellular Ca2+ions are exchanged against extracellular Na+ions (Ca2+efflux, forward mode). The decrease of intracellular Ca2+ions was detected by measuring the fluorescence of the calcium indicator dye at a wavelength of 520 nm by a FLIPR device.Briefly, similarly as for the reverse mode, for the forward mode transport assay 18000 cells per well were seeded into a 96 well microplate (Corning COSTAR 3904) and incubated overnight in culture medium (cf. above). A total volume of 100 ul medium per well was used.
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 460.56, ALogP 4.97, HBA 7, HBD 1, PSA 78.27, QED 0.44
Compound (SMILES): O=C(NCc1ccncc1)c1cnc(Oc2ccc3c(c2)CCC(c2cccc(F)c2)O3)s1
InChIKey: SNOIEIPMQYGTKA-UHFFFAOYSA-N
Target: Sodium/calcium exchanger 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32418
Assay: Forward Mode Assay: The assay is based on the monitoring of intracellular Ca2+concentrations using the PBX Calcium Assay Kit from BD (Becton, Dickinson and Company) with calcium indicator dye 51-9000177BKa (BD, 640177), CHO cells expressing NCX1 were loaded with the dye, and after a preincubation period with the test compound, lonomycin (Calbiochem, 407950) was added. Ionomycin is an ionophor for Ca2+ions mediating an increase of intracellular Ca2+ions. Consequently, intracellular Ca2+ions are exchanged against extracellular Na+ions (Ca2+efflux, forward mode). The decrease of intracellular Ca2+ions was detected by measuring the fluorescence of the calcium indicator dye at a wavelength of 520 nm by a FLIPR device.Briefly, similarly as for the reverse mode, for the forward mode transport assay 18000 cells per well were seeded into a 96 well microplate (Corning COSTAR 3904) and incubated overnight in culture medium (cf. above). A total volume of 100 ul medium per well was used.
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 461.52, ALogP 5.47, HBA 6, HBD 1, PSA 73.34, QED 0.41
Compound (SMILES): O=C(NCc1nnc2n1CCC2)c1cnc(Oc2ccc3c(c2)CCC(c2cccc(F)c2)O3)s1
InChIKey: IDVJLAHSRXEJMB-UHFFFAOYSA-N
Target: Sodium/calcium exchanger 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32418
Assay: Forward Mode Assay: The assay is based on the monitoring of intracellular Ca2+concentrations using the PBX Calcium Assay Kit from BD (Becton, Dickinson and Company) with calcium indicator dye 51-9000177BKa (BD, 640177), CHO cells expressing NCX1 were loaded with the dye, and after a preincubation period with the test compound, lonomycin (Calbiochem, 407950) was added. Ionomycin is an ionophor for Ca2+ions mediating an increase of intracellular Ca2+ions. Consequently, intracellular Ca2+ions are exchanged against extracellular Na+ions (Ca2+efflux, forward mode). The decrease of intracellular Ca2+ions was detected by measuring the fluorescence of the calcium indicator dye at a wavelength of 520 nm by a FLIPR device.Briefly, similarly as for the reverse mode, for the forward mode transport assay 18000 cells per well were seeded into a 96 well microplate (Corning COSTAR 3904) and incubated overnight in culture medium (cf. above). A total volume of 100 ul medium per well was used.
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 491.55, ALogP 4.61, HBA 8, HBD 1, PSA 91.16, QED 0.42
Compound (SMILES): O=C(NCc1ccnc(Cl)c1)c1cnc(Oc2ccc3c(c2)CCC(c2ccccc2)O3)s1
InChIKey: UZUNANKEQRRTHJ-UHFFFAOYSA-N
Target: Sodium/calcium exchanger 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32418
Assay: Forward Mode Assay: The assay is based on the monitoring of intracellular Ca2+concentrations using the PBX Calcium Assay Kit from BD (Becton, Dickinson and Company) with calcium indicator dye 51-9000177BKa (BD, 640177), CHO cells expressing NCX1 were loaded with the dye, and after a preincubation period with the test compound, lonomycin (Calbiochem, 407950) was added. Ionomycin is an ionophor for Ca2+ions mediating an increase of intracellular Ca2+ions. Consequently, intracellular Ca2+ions are exchanged against extracellular Na+ions (Ca2+efflux, forward mode). The decrease of intracellular Ca2+ions was detected by measuring the fluorescence of the calcium indicator dye at a wavelength of 520 nm by a FLIPR device.Briefly, similarly as for the reverse mode, for the forward mode transport assay 18000 cells per well were seeded into a 96 well microplate (Corning COSTAR 3904) and incubated overnight in culture medium (cf. above). A total volume of 100 ul medium per well was used.
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 477.97, ALogP 5.98, HBA 6, HBD 1, PSA 73.34, QED 0.35
Compound (SMILES): O=C(NCc1ccno1)c1cnc(Oc2ccc3c(c2)CCC(c2cccnc2)O3)s1
InChIKey: MWNLSPFRYZOYBO-UHFFFAOYSA-N
Target: Sodium/calcium exchanger 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32418
Assay: Forward Mode Assay: The assay is based on the monitoring of intracellular Ca2+concentrations using the PBX Calcium Assay Kit from BD (Becton, Dickinson and Company) with calcium indicator dye 51-9000177BKa (BD, 640177), CHO cells expressing NCX1 were loaded with the dye, and after a preincubation period with the test compound, lonomycin (Calbiochem, 407950) was added. Ionomycin is an ionophor for Ca2+ions mediating an increase of intracellular Ca2+ions. Consequently, intracellular Ca2+ions are exchanged against extracellular Na+ions (Ca2+efflux, forward mode). The decrease of intracellular Ca2+ions was detected by measuring the fluorescence of the calcium indicator dye at a wavelength of 520 nm by a FLIPR device.Briefly, similarly as for the reverse mode, for the forward mode transport assay 18000 cells per well were seeded into a 96 well microplate (Corning COSTAR 3904) and incubated overnight in culture medium (cf. above). A total volume of 100 ul medium per well was used.
Measurement: IC50 = 8300 nM (pChEMBL 5.079999923706055)
Descriptors: MW 434.48, ALogP 4.31, HBA 8, HBD 1, PSA 99.37, QED 0.48