lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCc1cccc(CC)c1NC(=O)c1cn(C)c2c1CCCc1cnc(Nc3ccc(N4CCN(C)CC4)cc3OC)nc1-2
InChIKey: CNSGSATYYDDERW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Kinase Inhibition Assay: The buffer for PIM-2 assay was composed of HEPES 50 mM, at pH 7.5, with 1 mM MgCl2, 1 mM DTT, 3 microM Na3VO4, and 0.2 mg/mL BSAFull-length human PIM-2 was expressed and purified as described in Fedorov O, et al., PNAS 2007 104, 51, 20523-28.Assay Conditions (Final Concentrations)Enzyme concentration=1.5 nMAktide substrate (Chemical Abstract Service Registry Number 324029-01-8)=5 microMATP=4 microM33P-Î³-ATP=1 nM.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 593.78, ALogP 5.85, HBA 8, HBD 2, PSA 87.55, QED 0.26
Compound (SMILES): CC(C)CC1(O)CN(C(=O)Nc2cc(Oc3ccc(F)cc3)cc(Oc3ccc(C(C)(C)C(=O)O)cc3)c2)C1
InChIKey: HKSAGIGRQWXHMH-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95136
Assay: Antagonist activity at S1P2 receptor (unknown origin) expressed in CHO cells assessed as inhibition of S1P-induced increase in intracellular calcium ion concentration by Fura-2AM based fluorescence analysis
Measurement: IC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 536.6, ALogP 6.4, HBA 5, HBD 3, PSA 108.33, QED 0.29
Compound (SMILES): COCc1cnn(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C2(CCC2)O3)c1
InChIKey: NRTIHHVWKLDASP-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 7200 nM (pChEMBL 5.139999866485596)
Descriptors: MW 396.45, ALogP 1.89, HBA 8, HBD 1, PSA 93.12, QED 0.85
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cncnc3)ccc1OC1(CCC1)C21COC1
InChIKey: APMDRJOSPMXZBV-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 590 nM (pChEMBL 6.230000019073486)
Descriptors: MW 364.4, ALogP 2.02, HBA 7, HBD 1, PSA 91.85, QED 0.83
Compound (SMILES): CC1(C)Oc2ccc(Br)cc2C2(COC(N)=N2)C12COC2
InChIKey: BFCFOLFRUMYREH-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 353.22, ALogP 2.18, HBA 5, HBD 1, PSA 66.07, QED 0.78
Compound (SMILES): CCC1Oc2ccc(Br)cc2C2(COC(N)=N2)C12COC2
InChIKey: UVKPJIHODHUWCZ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition Assay: The hERG potassium current was measured in a hERG-stably-expressing Chinese hamster ovary K1 (CHO) cells. The experiments were performed using an automated planar patch-clamp system QPatch HTX (Sophion Bioscience A/S). The application of pressure for forming gigaseals and whole-cell patch clamp configuration were established using the QPatch assay software. Patch-clamp experiments were performed in voltage-clamp mode and whole-cell currents were recorded. The following stimulation protocol was applied to investigate the effects of compounds on hERG potassium channel.The membrane potential was held at −80 mV and repetitively (every 15 seconds) depolarized to +20 mV for 4800 milliseconds after the pulse to −50 mV for 20 milliseconds served to define the baseline, followed by repolarizing step to −50 mV for 5000 milliseconds to evaluate of the tail current amplitude. Experiments were conducted at room temperature.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 353.22, ALogP 2.18, HBA 5, HBD 1, PSA 66.07, QED 0.84
Compound (SMILES): NC1=NC2(CO1)c1cc(Br)ccc1OC(Cc1ccccc1)C21COC1
InChIKey: GSLXZIRPXIIFQZ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition Assay: The hERG potassium current was measured in a hERG-stably-expressing Chinese hamster ovary K1 (CHO) cells. The experiments were performed using an automated planar patch-clamp system QPatch HTX (Sophion Bioscience A/S). The application of pressure for forming gigaseals and whole-cell patch clamp configuration were established using the QPatch assay software. Patch-clamp experiments were performed in voltage-clamp mode and whole-cell currents were recorded. The following stimulation protocol was applied to investigate the effects of compounds on hERG potassium channel.The membrane potential was held at −80 mV and repetitively (every 15 seconds) depolarized to +20 mV for 4800 milliseconds after the pulse to −50 mV for 20 milliseconds served to define the baseline, followed by repolarizing step to −50 mV for 5000 milliseconds to evaluate of the tail current amplitude. Experiments were conducted at room temperature.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 415.29, ALogP 3.01, HBA 5, HBD 1, PSA 66.07, QED 0.82
Compound (SMILES): NC1=NC2(CO1)c1cc(Br)ccc1OC(CC1CC1)C21COC1
InChIKey: FKWYDOXONAHPDE-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition Assay: The hERG potassium current was measured in a hERG-stably-expressing Chinese hamster ovary K1 (CHO) cells. The experiments were performed using an automated planar patch-clamp system QPatch HTX (Sophion Bioscience A/S). The application of pressure for forming gigaseals and whole-cell patch clamp configuration were established using the QPatch assay software. Patch-clamp experiments were performed in voltage-clamp mode and whole-cell currents were recorded. The following stimulation protocol was applied to investigate the effects of compounds on hERG potassium channel.The membrane potential was held at −80 mV and repetitively (every 15 seconds) depolarized to +20 mV for 4800 milliseconds after the pulse to −50 mV for 20 milliseconds served to define the baseline, followed by repolarizing step to −50 mV for 5000 milliseconds to evaluate of the tail current amplitude. Experiments were conducted at room temperature.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 379.25, ALogP 2.57, HBA 5, HBD 1, PSA 66.07, QED 0.86
Compound (SMILES): CC1(C)Oc2ccc(NC(=O)c3ccc(Cl)cn3)cc2C2(COC(N)=N2)C12COC2
InChIKey: INWIVMOTHPFWNU-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition Assay: The hERG potassium current was measured in a hERG-stably-expressing Chinese hamster ovary K1 (CHO) cells. The experiments were performed using an automated planar patch-clamp system QPatch HTX (Sophion Bioscience A/S). The application of pressure for forming gigaseals and whole-cell patch clamp configuration were established using the QPatch assay software. Patch-clamp experiments were performed in voltage-clamp mode and whole-cell currents were recorded. The following stimulation protocol was applied to investigate the effects of compounds on hERG potassium channel.The membrane potential was held at −80 mV and repetitively (every 15 seconds) depolarized to +20 mV for 4800 milliseconds after the pulse to −50 mV for 20 milliseconds served to define the baseline, followed by repolarizing step to −50 mV for 5000 milliseconds to evaluate of the tail current amplitude. Experiments were conducted at room temperature.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 428.88, ALogP 2.72, HBA 7, HBD 2, PSA 108.06, QED 0.76
Compound (SMILES): CC1(C)Oc2ccc(NC(=O)c3ccc(F)cn3)cc2C2(COC(N)=N2)C12COC2
InChIKey: FSJTVQBTRXXXMC-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition Assay: The hERG potassium current was measured in a hERG-stably-expressing Chinese hamster ovary K1 (CHO) cells. The experiments were performed using an automated planar patch-clamp system QPatch HTX (Sophion Bioscience A/S). The application of pressure for forming gigaseals and whole-cell patch clamp configuration were established using the QPatch assay software. Patch-clamp experiments were performed in voltage-clamp mode and whole-cell currents were recorded. The following stimulation protocol was applied to investigate the effects of compounds on hERG potassium channel.The membrane potential was held at −80 mV and repetitively (every 15 seconds) depolarized to +20 mV for 4800 milliseconds after the pulse to −50 mV for 20 milliseconds served to define the baseline, followed by repolarizing step to −50 mV for 5000 milliseconds to evaluate of the tail current amplitude. Experiments were conducted at room temperature.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.42, ALogP 2.2, HBA 7, HBD 2, PSA 108.06, QED 0.78
Compound (SMILES): NC1=NC2(CO1)c1cc(NC(=O)c3ncc(Cl)cc3F)ccc1OCC21CC1
InChIKey: BAZZVTQQQIAGLD-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition Assay: The hERG potassium current was measured in a hERG-stably-expressing Chinese hamster ovary K1 (CHO) cells. The experiments were performed using an automated planar patch-clamp system QPatch HTX (Sophion Bioscience A/S). The application of pressure for forming gigaseals and whole-cell patch clamp configuration were established using the QPatch assay software. Patch-clamp experiments were performed in voltage-clamp mode and whole-cell currents were recorded. The following stimulation protocol was applied to investigate the effects of compounds on hERG potassium channel.The membrane potential was held at −80 mV and repetitively (every 15 seconds) depolarized to +20 mV for 4800 milliseconds after the pulse to −50 mV for 20 milliseconds served to define the baseline, followed by repolarizing step to −50 mV for 5000 milliseconds to evaluate of the tail current amplitude. Experiments were conducted at room temperature.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 402.81, ALogP 2.84, HBA 6, HBD 2, PSA 98.83, QED 0.8
Compound (SMILES): CC1(C)Oc2ccc(NC(=O)c3ncc(Cl)cc3F)cc2C2(COC(N)=N2)C12COC2
InChIKey: NNCFJTIUQAEALJ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition Assay: The hERG potassium current was measured in a hERG-stably-expressing Chinese hamster ovary K1 (CHO) cells. The experiments were performed using an automated planar patch-clamp system QPatch HTX (Sophion Bioscience A/S). The application of pressure for forming gigaseals and whole-cell patch clamp configuration were established using the QPatch assay software. Patch-clamp experiments were performed in voltage-clamp mode and whole-cell currents were recorded. The following stimulation protocol was applied to investigate the effects of compounds on hERG potassium channel.The membrane potential was held at −80 mV and repetitively (every 15 seconds) depolarized to +20 mV for 4800 milliseconds after the pulse to −50 mV for 20 milliseconds served to define the baseline, followed by repolarizing step to −50 mV for 5000 milliseconds to evaluate of the tail current amplitude. Experiments were conducted at room temperature.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 446.87, ALogP 2.85, HBA 7, HBD 2, PSA 108.06, QED 0.73
Compound (SMILES): NC1=NC2(CO1)c1cc(NC(=O)c3ccc(F)cn3)ccc1OCC21CC1
InChIKey: SGURBDAGQXAXNV-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition Assay: The hERG potassium current was measured in a hERG-stably-expressing Chinese hamster ovary K1 (CHO) cells. The experiments were performed using an automated planar patch-clamp system QPatch HTX (Sophion Bioscience A/S). The application of pressure for forming gigaseals and whole-cell patch clamp configuration were established using the QPatch assay software. Patch-clamp experiments were performed in voltage-clamp mode and whole-cell currents were recorded. The following stimulation protocol was applied to investigate the effects of compounds on hERG potassium channel.The membrane potential was held at −80 mV and repetitively (every 15 seconds) depolarized to +20 mV for 4800 milliseconds after the pulse to −50 mV for 20 milliseconds served to define the baseline, followed by repolarizing step to −50 mV for 5000 milliseconds to evaluate of the tail current amplitude. Experiments were conducted at room temperature.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 368.37, ALogP 2.19, HBA 6, HBD 2, PSA 98.83, QED 0.85
Compound (SMILES): NC1=NC2(CO1)c1cc(NC(=O)c3ccc(Cl)cn3)ccc1OCC21CC1
InChIKey: ASXIBZVBBQRBMI-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition Assay: The hERG potassium current was measured in a hERG-stably-expressing Chinese hamster ovary K1 (CHO) cells. The experiments were performed using an automated planar patch-clamp system QPatch HTX (Sophion Bioscience A/S). The application of pressure for forming gigaseals and whole-cell patch clamp configuration were established using the QPatch assay software. Patch-clamp experiments were performed in voltage-clamp mode and whole-cell currents were recorded. The following stimulation protocol was applied to investigate the effects of compounds on hERG potassium channel.The membrane potential was held at −80 mV and repetitively (every 15 seconds) depolarized to +20 mV for 4800 milliseconds after the pulse to −50 mV for 20 milliseconds served to define the baseline, followed by repolarizing step to −50 mV for 5000 milliseconds to evaluate of the tail current amplitude. Experiments were conducted at room temperature.
Measurement: IC50 = 2170 nM (pChEMBL 5.659999847412109)
Descriptors: MW 384.82, ALogP 2.7, HBA 6, HBD 2, PSA 98.83, QED 0.83
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cc(Cl)cnc3F)ccc1OCC21COC1
InChIKey: OXWANDFSWNCOLM-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 375.79, ALogP 2.49, HBA 6, HBD 1, PSA 78.96, QED 0.77
Compound (SMILES): CC1(C)Oc2ccc(Br)cc2C2(CSC(N)=N2)C12COC2
InChIKey: FXWBDJSWBRAHBD-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 369.28, ALogP 2.89, HBA 5, HBD 1, PSA 56.84, QED 0.76
Compound (SMILES): NC1=NC2(CO1)c1cc(Nc3ncccc3Cl)ccc1OCC21COC1
InChIKey: XNPBNQHTEMDPQV-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 372.81, ALogP 2.43, HBA 7, HBD 2, PSA 90.99, QED 0.84
Compound (SMILES): COc1cccnc1Nc1ccc2c(c1)C1(COC(N)=N1)C1(COC1)C1(CCC1)O2
InChIKey: WWHBQSJSWHAQSI-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 408.46, ALogP 2.71, HBA 8, HBD 2, PSA 100.22, QED 0.81
Compound (SMILES): CC(C)Cc1ccc2c(c1)C1(COC(N)=N1)C1(COC1)C1(CCC1)O2
InChIKey: DRTDEDKNDXQLDZ-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 342.44, ALogP 2.76, HBA 5, HBD 1, PSA 66.07, QED 0.9
Compound (SMILES): CC1(C)Oc2ccc(-c3cncnc3)cc2C2(COC(N)=N2)C12COC2
InChIKey: WRPYZOUQPVZQFZ-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 172 nM (pChEMBL 6.760000228881836)
Descriptors: MW 352.39, ALogP 1.87, HBA 7, HBD 1, PSA 91.85, QED 0.84
Compound (SMILES): CC#Cc1cncc(-c2ccc3c(c2)C2(COC(N)=N2)C2(CC2)CO3)c1
InChIKey: ZKVKPYPCNDJJIH-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: IC50 = 287 nM (pChEMBL 6.539999961853027)
Descriptors: MW 345.4, ALogP 2.83, HBA 5, HBD 1, PSA 69.73, QED 0.81
Compound (SMILES): CC#Cc1cncc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)CO3)c1
InChIKey: KPXCLUUQECRYFF-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Potency of test compounds were determined by measurement of their inhibition of BACE1 activity toward a fluorescent substrate. Experiments were performed by reference to the procedure as described in Ermolieff, et al. (Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety). Briefly, the recombinant protease unit of BACE1 was prepared from E. coli expression as inclusion bodies, refolded, and purified as described in Lin, et al., (Proc. Nat. Acad. Sci. 97:1456-1460 (2000)). Fluorogenic substrate, MCA-SEVNLDAEFK(DNP)-NH2 (SEQ ID NO:1) was purchased. (M-2485, Bachem Americas, Torrance, Calif.). The substrate was derived from 10 amino acids of the human amyloid precursor protein (APP), with the Swedish variant amino acids at the beta-secretase cleavage site. The terminal amino acid was modified from arginine to lysine to facilitate derivatization with a functional group for detection by autofluorescence.
Measurement: Ki = 354 nM (pChEMBL 6.449999809265137)
Descriptors: MW 361.4, ALogP 2.07, HBA 6, HBD 1, PSA 78.96, QED 0.79
Compound (SMILES): CC1(C)Oc2ccc(-c3cncnc3)cc2C2(CSC(N)=N2)C12COC2
InChIKey: DGIBRPPLNYXLMV-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 368.46, ALogP 2.59, HBA 7, HBD 1, PSA 82.62, QED 0.83
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cncc(C4CC4)c3)ccc1OCC21CC1
InChIKey: DFEWHEYFZREFMD-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 610 nM (pChEMBL 6.210000038146973)
Descriptors: MW 347.42, ALogP 3.34, HBA 5, HBD 1, PSA 69.73, QED 0.9
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cncc(OCC(F)(F)F)c3)ccc1OCC21CC1
InChIKey: PBIVNBDJISSSOF-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 405.38, ALogP 3.4, HBA 6, HBD 1, PSA 78.96, QED 0.85
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cncc(OCC(F)F)c3)ccc1OCC21CC1
InChIKey: WQKBRYBBAYLSSQ-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 387.39, ALogP 3.11, HBA 6, HBD 1, PSA 78.96, QED 0.87
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cncc(OC(F)F)c3)ccc1OCC21CC1
InChIKey: UNYXJDJEOAZPJZ-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 373.36, ALogP 3.06, HBA 6, HBD 1, PSA 78.96, QED 0.89
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cnc4[nH]cc(Cl)c4c3)ccc1OCC21CC1
InChIKey: OJCJILDVNFWSDR-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 380.83, ALogP 3.6, HBA 5, HBD 2, PSA 85.52, QED 0.68
Compound (SMILES): CCc1cncc(-c2ccc3c(c2)C2(COC(N)=N2)C2(CC2)CO3)c1
InChIKey: ACFKJXYIJBZGDF-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 335.41, ALogP 3.02, HBA 5, HBD 1, PSA 69.73, QED 0.92
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cncc(OCC(F)(F)C(F)F)c3)ccc1OCC21CC1
InChIKey: DSXZHBCAGPUTHY-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 437.39, ALogP 3.74, HBA 6, HBD 1, PSA 78.96, QED 0.72
Compound (SMILES): COc1ccnc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C(C)(C)O3)c1
InChIKey: VODDOGVAQARPID-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 381.43, ALogP 2.48, HBA 7, HBD 1, PSA 88.19, QED 0.86
Compound (SMILES): CC#Cc1cncc(-c2ccc3c(c2)C2(CSC(N)=N2)C2(COC2)CO3)c1
InChIKey: SUTVFEFTMJCRDP-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 377.47, ALogP 2.79, HBA 6, HBD 1, PSA 69.73, QED 0.77
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cncc(F)c3)ccc1OC1(CCC1)C21COC1
InChIKey: VKXZBNSASBAXPO-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 960 nM (pChEMBL 6.019999980926514)
Descriptors: MW 381.41, ALogP 2.76, HBA 6, HBD 1, PSA 78.96, QED 0.82
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cccnc3F)ccc1OC1(CCC1)C21COC1
InChIKey: MIWGEPYDEJPCPW-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 381.41, ALogP 2.76, HBA 6, HBD 1, PSA 78.96, QED 0.77
Compound (SMILES): COc1cncc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C2(CCC2)O3)c1
InChIKey: OKGLRFINLNSCOR-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 393.44, ALogP 2.63, HBA 7, HBD 1, PSA 88.19, QED 0.84
Compound (SMILES): Cc1cncc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C2(CCC2)O3)c1
InChIKey: XVSNEAWVASTHHT-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 377.44, ALogP 2.93, HBA 6, HBD 1, PSA 78.96, QED 0.83