lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC1(C)Oc2ccc(-c3ccc4[nH]ccc4c3)cc2C2(COC(N)=N2)C12COC2
InChIKey: VVFPODWCIIZSFT-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: Potency of compounds were also measured using another fluorogenic substrate, TruPoint BACE1 Substrate Eu-CEVNLDAEFK-QSY 7 (SEQ ID NO:3) (AD0258, PerkinElmer, Boston Mass.). This substrate also has Swedish variant amino acids at the β-secretase cleavage site, with a fluorescent europium (Eu) chelate coupled to one end and a quencher of europium fluorescence (QSY7) coupled to the other end via lysine. If the sample contains BACE1 activity, the Eu chelate and the quencher will be separated as the substrate is cleaved. The Eu-signal increases and it can be measured by time-resolved fluorometry, EnVision, 30 minutes after the substrate (final concentration 300 nM) was added.
Measurement: IC50 = 2180 nM (pChEMBL 5.659999847412109)
Descriptors: MW 389.46, ALogP 3.56, HBA 5, HBD 2, PSA 81.86, QED 0.67
Compound (SMILES): CC1(C)Oc2ccc(-c3cccc4cc[nH]c34)cc2C2(COC(N)=N2)C12COC2
InChIKey: YPBRRBIMXWDWLH-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: Potency of compounds were also measured using another fluorogenic substrate, TruPoint BACE1 Substrate Eu-CEVNLDAEFK-QSY 7 (SEQ ID NO:3) (AD0258, PerkinElmer, Boston Mass.). This substrate also has Swedish variant amino acids at the β-secretase cleavage site, with a fluorescent europium (Eu) chelate coupled to one end and a quencher of europium fluorescence (QSY7) coupled to the other end via lysine. If the sample contains BACE1 activity, the Eu chelate and the quencher will be separated as the substrate is cleaved. The Eu-signal increases and it can be measured by time-resolved fluorometry, EnVision, 30 minutes after the substrate (final concentration 300 nM) was added.
Measurement: IC50 = 1550 nM (pChEMBL 5.809999942779541)
Descriptors: MW 389.46, ALogP 3.56, HBA 5, HBD 2, PSA 81.86, QED 0.67
Compound (SMILES): CC1(C)Oc2ccc(-c3cccc4[nH]ncc34)cc2C2(COC(N)=N2)C12COC2
InChIKey: DESFPGMIDIOQPB-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 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 390.44, ALogP 2.96, HBA 6, HBD 2, PSA 94.75, QED 0.67
Compound (SMILES): CC1(C)Oc2ccc(-c3ccc4[nH]ncc4c3)cc2C2(COC(N)=N2)C12COC2
InChIKey: WSZIQFROVOJHOO-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 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 390.44, ALogP 2.96, HBA 6, HBD 2, PSA 94.75, QED 0.67
Compound (SMILES): CC1(C)Oc2ccc(-c3ccc4nonc4c3)cc2C2(COC(N)=N2)C12COC2
InChIKey: PKUHVJVJHBYAMJ-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: Potency of compounds were also measured using another fluorogenic substrate, TruPoint BACE1 Substrate Eu-CEVNLDAEFK-QSY 7 (SEQ ID NO:3) (AD0258, PerkinElmer, Boston Mass.). This substrate also has Swedish variant amino acids at the β-secretase cleavage site, with a fluorescent europium (Eu) chelate coupled to one end and a quencher of europium fluorescence (QSY7) coupled to the other end via lysine. If the sample contains BACE1 activity, the Eu chelate and the quencher will be separated as the substrate is cleaved. The Eu-signal increases and it can be measured by time-resolved fluorometry, EnVision, 30 minutes after the substrate (final concentration 300 nM) was added.
Measurement: IC50 = 747 nM (pChEMBL 6.130000114440918)
Descriptors: MW 392.42, ALogP 2.62, HBA 8, HBD 1, PSA 104.99, QED 0.68
Compound (SMILES): CC1(C)Oc2ccc(-c3cccc4cccnc34)cc2C2(COC(N)=N2)C12COC2
InChIKey: VJBWMBRNRXJSBA-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: Potency of compounds were also measured using another fluorogenic substrate, TruPoint BACE1 Substrate Eu-CEVNLDAEFK-QSY 7 (SEQ ID NO:3) (AD0258, PerkinElmer, Boston Mass.). This substrate also has Swedish variant amino acids at the β-secretase cleavage site, with a fluorescent europium (Eu) chelate coupled to one end and a quencher of europium fluorescence (QSY7) coupled to the other end via lysine. If the sample contains BACE1 activity, the Eu chelate and the quencher will be separated as the substrate is cleaved. The Eu-signal increases and it can be measured by time-resolved fluorometry, EnVision, 30 minutes after the substrate (final concentration 300 nM) was added.
Measurement: IC50 = 2060 nM (pChEMBL 5.690000057220459)
Descriptors: MW 401.47, ALogP 3.63, HBA 6, HBD 1, PSA 78.96, QED 0.67
Compound (SMILES): CC1(C)Oc2ccc(-c3cccc4cnccc34)cc2C2(COC(N)=N2)C12COC2
InChIKey: BKDQSRMNJPVQTC-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: Potency of compounds were also measured using another fluorogenic substrate, TruPoint BACE1 Substrate Eu-CEVNLDAEFK-QSY 7 (SEQ ID NO:3) (AD0258, PerkinElmer, Boston Mass.). This substrate also has Swedish variant amino acids at the β-secretase cleavage site, with a fluorescent europium (Eu) chelate coupled to one end and a quencher of europium fluorescence (QSY7) coupled to the other end via lysine. If the sample contains BACE1 activity, the Eu chelate and the quencher will be separated as the substrate is cleaved. The Eu-signal increases and it can be measured by time-resolved fluorometry, EnVision, 30 minutes after the substrate (final concentration 300 nM) was added.
Measurement: IC50 = 1770 nM (pChEMBL 5.75)
Descriptors: MW 401.47, ALogP 3.63, HBA 6, HBD 1, PSA 78.96, QED 0.67
Compound (SMILES): COC/C=C/c1ccc2c(c1)C1(COC(N)=N1)C1(COC1)C(C)(C)O2
InChIKey: INLZNNXNRQPRBS-SNAWJCMRSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: Potency of compounds were also measured using another fluorogenic substrate, TruPoint BACE1 Substrate Eu-CEVNLDAEFK-QSY 7 (SEQ ID NO:3) (AD0258, PerkinElmer, Boston Mass.). This substrate also has Swedish variant amino acids at the β-secretase cleavage site, with a fluorescent europium (Eu) chelate coupled to one end and a quencher of europium fluorescence (QSY7) coupled to the other end via lysine. If the sample contains BACE1 activity, the Eu chelate and the quencher will be separated as the substrate is cleaved. The Eu-signal increases and it can be measured by time-resolved fluorometry, EnVision, 30 minutes after the substrate (final concentration 300 nM) was added.
Measurement: IC50 = 2130 nM (pChEMBL 5.670000076293945)
Descriptors: MW 344.41, ALogP 2.07, HBA 6, HBD 1, PSA 75.3, QED 0.91
Compound (SMILES): CC1(C)Oc2ccc(-c3ccc4c(c3)OCO4)cc2C2(COC(N)=N2)C12COC2
InChIKey: WDLWOGRZCRSSNH-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 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 394.43, ALogP 2.81, HBA 7, HBD 1, PSA 84.53, QED 0.8
Compound (SMILES): CC1(C)Oc2ccc(-c3cccc(OC(F)(F)F)c3)cc2C2(COC(N)=N2)C12COC2
InChIKey: QIAHDRDUKXPIPE-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: Potency of compounds were also measured using another fluorogenic substrate, TruPoint BACE1 Substrate Eu-CEVNLDAEFK-QSY 7 (SEQ ID NO:3) (AD0258, PerkinElmer, Boston Mass.). This substrate also has Swedish variant amino acids at the β-secretase cleavage site, with a fluorescent europium (Eu) chelate coupled to one end and a quencher of europium fluorescence (QSY7) coupled to the other end via lysine. If the sample contains BACE1 activity, the Eu chelate and the quencher will be separated as the substrate is cleaved. The Eu-signal increases and it can be measured by time-resolved fluorometry, EnVision, 30 minutes after the substrate (final concentration 300 nM) was added.
Measurement: IC50 = 880 nM (pChEMBL 6.059999942779541)
Descriptors: MW 434.41, ALogP 3.98, HBA 6, HBD 1, PSA 75.3, QED 0.77
Compound (SMILES): CC1(C)Oc2ccc(-c3ccccc3OC(F)(F)F)cc2C2(COC(N)=N2)C12COC2
InChIKey: DXUBDEWFIYBFBX-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: Potency of compounds were also measured using another fluorogenic substrate, TruPoint BACE1 Substrate Eu-CEVNLDAEFK-QSY 7 (SEQ ID NO:3) (AD0258, PerkinElmer, Boston Mass.). This substrate also has Swedish variant amino acids at the β-secretase cleavage site, with a fluorescent europium (Eu) chelate coupled to one end and a quencher of europium fluorescence (QSY7) coupled to the other end via lysine. If the sample contains BACE1 activity, the Eu chelate and the quencher will be separated as the substrate is cleaved. The Eu-signal increases and it can be measured by time-resolved fluorometry, EnVision, 30 minutes after the substrate (final concentration 300 nM) was added.
Measurement: IC50 = 2720 nM (pChEMBL 5.570000171661377)
Descriptors: MW 434.41, ALogP 3.98, HBA 6, HBD 1, PSA 75.3, QED 0.77
Compound (SMILES): CC1(C)Oc2ccc(-c3c(F)ccc(F)c3F)cc2C2(COC(N)=N2)C12COC2
InChIKey: MDDVTIQXTKOMRK-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: Potency of compounds were also measured using another fluorogenic substrate, TruPoint BACE1 Substrate Eu-CEVNLDAEFK-QSY 7 (SEQ ID NO:3) (AD0258, PerkinElmer, Boston Mass.). This substrate also has Swedish variant amino acids at the β-secretase cleavage site, with a fluorescent europium (Eu) chelate coupled to one end and a quencher of europium fluorescence (QSY7) coupled to the other end via lysine. If the sample contains BACE1 activity, the Eu chelate and the quencher will be separated as the substrate is cleaved. The Eu-signal increases and it can be measured by time-resolved fluorometry, EnVision, 30 minutes after the substrate (final concentration 300 nM) was added.
Measurement: IC50 = 1270 nM (pChEMBL 5.900000095367432)
Descriptors: MW 404.39, ALogP 3.5, HBA 5, HBD 1, PSA 66.07, QED 0.74
Compound (SMILES): CC1(C)Oc2ccc(-c3ccc(OC(F)F)cc3)cc2C2(COC(N)=N2)C12COC2
InChIKey: DBMWNPACPWCFOJ-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Time Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: Potency of compounds were also measured using another fluorogenic substrate, TruPoint BACE1 Substrate Eu-CEVNLDAEFK-QSY 7 (SEQ ID NO:3) (AD0258, PerkinElmer, Boston Mass.). This substrate also has Swedish variant amino acids at the β-secretase cleavage site, with a fluorescent europium (Eu) chelate coupled to one end and a quencher of europium fluorescence (QSY7) coupled to the other end via lysine. If the sample contains BACE1 activity, the Eu chelate and the quencher will be separated as the substrate is cleaved. The Eu-signal increases and it can be measured by time-resolved fluorometry, EnVision, 30 minutes after the substrate (final concentration 300 nM) was added.
Measurement: IC50 = 1920 nM (pChEMBL 5.71999979019165)
Descriptors: MW 416.42, ALogP 3.68, HBA 6, HBD 1, PSA 75.3, QED 0.83
Compound (SMILES): NC1=NC2(CO1)c1cc(Br)ccc1OCC21CC(F)(F)C1
InChIKey: UWKRYKVCCZEOQP-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 359.17, ALogP 2.8, HBA 4, HBD 1, PSA 56.84, QED 0.78
Compound (SMILES): NC1=NC2(CO1)c1cc(NC(=O)c3ncc(Br)cn3)ccc1OCC21CC1
InChIKey: RUPHOSKJXJYHAD-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 = 661 nM (pChEMBL 6.179999828338623)
Descriptors: MW 430.26, ALogP 2.2, HBA 7, HBD 2, PSA 111.72, QED 0.76
Compound (SMILES): CC1(C)Oc2ccc(NC(=O)c3ncc(Br)cn3)cc2C2(COC(N)=N2)C12COC2
InChIKey: OKNLKKUCXCACGI-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 = 125 nM (pChEMBL 6.900000095367432)
Descriptors: MW 474.32, ALogP 2.22, HBA 8, HBD 2, PSA 120.95, QED 0.68
Compound (SMILES): Cc1cc(C#N)cnc1C(=O)Nc1ccc2c(c1)C1(COC(N)=N1)C1(CC1)CO2
InChIKey: LUKKVICWYPMUPG-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 = 248 nM (pChEMBL 6.610000133514404)
Descriptors: MW 389.42, ALogP 2.23, HBA 7, HBD 2, PSA 122.62, QED 0.81
Compound (SMILES): N#Cc1cnc(C(=O)Nc2ccc3c(c2)C2(COC(N)=N2)C2(CC2)CO3)c(Cl)c1
InChIKey: OBYNGUKQVYJXLG-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 = 318 nM (pChEMBL 6.5)
Descriptors: MW 409.83, ALogP 2.57, HBA 7, HBD 2, PSA 122.62, QED 0.79
Compound (SMILES): COc1cnc(C(=O)Nc2ccc3c(c2)C2(COC(N)=N2)C2(CC2)CO3)cn1
InChIKey: IPNOFVHQRLOFQU-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 381.39, ALogP 1.45, HBA 8, HBD 2, PSA 120.95, QED 0.83
Compound (SMILES): Cc1cc(Cl)cnc1C(=O)Nc1ccc2c(c1)C1(COC(N)=N1)C1(CC1)CO2
InChIKey: UGPKGDXAPPRVIR-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 = 349 nM (pChEMBL 6.460000038146973)
Descriptors: MW 398.85, ALogP 3.01, HBA 6, HBD 2, PSA 98.83, QED 0.81
Compound (SMILES): Cc1cc(Cl)cnc1C(=O)Nc1ccc2c(c1)C1(COC(N)=N1)C1(COC1)C(C)(C)O2
InChIKey: WTTPTTMLIGTSRC-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 = 109 nM (pChEMBL 6.960000038146973)
Descriptors: MW 442.9, ALogP 3.02, HBA 7, HBD 2, PSA 108.06, QED 0.74
Compound (SMILES): N#Cc1ccc(C(=O)Nc2ccc3c(c2)C2(COC(N)=N2)C2(CC2)CO3)nc1
InChIKey: FCSDLAQZROWWFP-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 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 375.39, ALogP 1.92, HBA 7, HBD 2, PSA 122.62, QED 0.83
Compound (SMILES): CC1(C)Oc2ccc(NC(=O)c3ccc(C#N)cn3)cc2C2(COC(N)=N2)C12COC2
InChIKey: GPWZMCGYHYETLO-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 = 118 nM (pChEMBL 6.929999828338623)
Descriptors: MW 419.44, ALogP 1.93, HBA 8, HBD 2, PSA 131.85, QED 0.76
Compound (SMILES): NC1=NC2(c3cc(-c4cncnc4)ccc3OCC23CC3)C(F)(F)CS1
InChIKey: UMLIDFYGFDMIGZ-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 > 1000 nM (pChEMBL 6)
Descriptors: MW 374.42, ALogP 3.21, HBA 6, HBD 1, PSA 73.39, QED 0.83
Compound (SMILES): NC1=NC2(c3cc(-c4cncnc4)ccc3OCC23CC3)c2cccc(F)c21
InChIKey: LEFCQXUNQUOKDG-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 = 4250 nM (pChEMBL 5.369999885559082)
Descriptors: MW 372.4, ALogP 3.42, HBA 5, HBD 1, PSA 73.39, QED 0.71
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cncnc3)ccc1OC(Cc1ccccc1)C21COC1
InChIKey: STMXAUVFLJMWDN-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 = 128 nM (pChEMBL 6.889999866485596)
Descriptors: MW 414.47, ALogP 2.7, HBA 7, HBD 1, PSA 91.85, QED 0.71
Compound (SMILES): CC#Cc1cncc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C(Cc2ccccc2)O3)c1
InChIKey: UZRCBYZWOAYXCE-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 = 113 nM (pChEMBL 6.949999809265137)
Descriptors: MW 451.53, ALogP 3.68, HBA 6, HBD 1, PSA 78.96, QED 0.61
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cncnc3)ccc1OC(CC1CC1)C21COC1
InChIKey: MSVXPEWIJQOLDG-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 = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 378.43, ALogP 2.26, HBA 7, HBD 1, PSA 91.85, QED 0.88
Compound (SMILES): CC#Cc1cncc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C(CC2CC2)O3)c1
InChIKey: KJZOKUPYIWIFKS-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 = 126 nM (pChEMBL 6.900000095367432)
Descriptors: MW 415.49, ALogP 3.24, HBA 6, HBD 1, PSA 78.96, QED 0.78
Compound (SMILES): NC1=NC2(c3cc(-c4cncnc4)ccc3OCC23CC3)C(F)(F)CO1
InChIKey: QZZCXMLMCPDROH-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 358.35, ALogP 2.49, HBA 6, HBD 1, PSA 82.62, QED 0.85
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cncnc3)ccc1OCC21CC(F)(F)C1
InChIKey: IBQLKXDWVJSRDU-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 358.35, ALogP 2.49, HBA 6, HBD 1, PSA 82.62, QED 0.85
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cccnc3)ccc1OC1(CCC1)C21COC1
InChIKey: MJGALTWQDCBMQD-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 363.42, ALogP 2.62, HBA 6, HBD 1, PSA 78.96, QED 0.84
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cncc4ccccc34)ccc1OC1(CCC1)C21COC1
InChIKey: NFVBGAGTKRCWGE-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 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 413.48, ALogP 3.77, HBA 6, HBD 1, PSA 78.96, QED 0.66
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cccnc3C(F)(F)F)ccc1OC1(CCC1)C21COC1
InChIKey: XPOQBFAIFSUYIN-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 431.41, ALogP 3.64, HBA 6, HBD 1, PSA 78.96, QED 0.75
Compound (SMILES): Cn1cc2cc(-c3ccc4c(c3)C3(COC(N)=N3)C3(CC3)CO4)ccc2n1
InChIKey: LYIYOHNNHUSMFQ-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 360.42, ALogP 2.95, HBA 6, HBD 1, PSA 74.66, QED 0.72
Compound (SMILES): NC1=NC2(COC1)c1cc(-c3cncnc3)ccc1OCC21CC1
InChIKey: AMQPJZMLPSZGED-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 322.37, ALogP 1.9, HBA 6, HBD 1, PSA 82.62, QED 0.87
Compound (SMILES): CC1(C)Oc2ccc(NC(=O)c3ccc(Cl)cn3)cc2[C@@]2(COC(N)=N2)C12COC2
InChIKey: INWIVMOTHPFWNU-NRFANRHFSA-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 = 44.7 nM (pChEMBL 7.349999904632568)
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(Br)cn3)cc2[C@@]2(COC(N)=N2)C12COC2
InChIKey: CWCLNAMDVBTHAU-NRFANRHFSA-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 = 44.4 nM (pChEMBL 7.349999904632568)
Descriptors: MW 473.33, ALogP 2.82, HBA 7, HBD 2, PSA 108.06, QED 0.69
Compound (SMILES): COc1cnc(C(=O)Nc2ccc3c(c2)[C@@]2(COC(N)=N2)C2(COC2)C(C)(C)O3)cn1
InChIKey: WZWNQLAVZZUSHH-NRFANRHFSA-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 = 76.5 nM (pChEMBL 7.119999885559082)
Descriptors: MW 425.45, ALogP 1.47, HBA 9, HBD 2, PSA 130.18, QED 0.76