lovingscience/chembl-v37-raw-activities huggingface dataset:
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: 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 = 2590 nM (pChEMBL 5.590000152587891)
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: 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 = 1450 nM (pChEMBL 5.840000152587891)
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: 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 = 1080 nM (pChEMBL 5.96999979019165)
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: 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 = 2820 nM (pChEMBL 5.550000190734863)
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: 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 = 2050 nM (pChEMBL 5.690000057220459)
Descriptors: MW 404.39, ALogP 3.5, HBA 5, HBD 1, PSA 66.07, QED 0.74
Compound (SMILES): CC1(C)Oc2ccc(-c3cccc4[nH]ccc34)cc2C2(COC(N)=N2)C12COC2
InChIKey: CFHBBNFAJNZTAI-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 = 2420 nM (pChEMBL 5.619999885559082)
Descriptors: MW 389.46, ALogP 3.56, HBA 5, HBD 2, PSA 81.86, QED 0.67
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: 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 = 3160 nM (pChEMBL 5.5)
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: 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 = 50600 nM (pChEMBL 4.300000190734863)
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: Ki = 623 nM (pChEMBL 6.210000038146973)
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: Ki = 83.5 nM (pChEMBL 7.079999923706055)
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: Ki = 215 nM (pChEMBL 6.670000076293945)
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: Ki = 280 nM (pChEMBL 6.550000190734863)
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: 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 = 1040 nM (pChEMBL 5.980000019073486)
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: Ki = 313 nM (pChEMBL 6.5)
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: Ki = 64.5 nM (pChEMBL 7.190000057220459)
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: Ki = 342 nM (pChEMBL 6.46999979019165)
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: Ki = 72 nM (pChEMBL 7.139999866485596)
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: 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 = 14900 nM (pChEMBL 4.829999923706055)
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: 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 = 736 nM (pChEMBL 6.130000114440918)
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: Ki = 92.1 nM (pChEMBL 7.039999961853027)
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: Ki = 71.1 nM (pChEMBL 7.150000095367432)
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 = 388 nM (pChEMBL 6.409999847412109)
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: Ki = 82.5 nM (pChEMBL 7.079999923706055)
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: 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 = 4910 nM (pChEMBL 5.309999942779541)
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: 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 = 7760 nM (pChEMBL 5.110000133514404)
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: 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 = 2000 nM (pChEMBL 5.699999809265137)
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: 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 = 4950 nM (pChEMBL 5.300000190734863)
Descriptors: MW 413.48, ALogP 3.77, HBA 6, HBD 1, PSA 78.96, QED 0.66
Compound (SMILES): NC1=NC2(CO1)c1cc(-c3cnc4ccccc4c3)ccc1OC1(CCC1)C21COC1
InChIKey: NXLOZNMRWJNNJD-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 = 19400 nM (pChEMBL 4.710000038146973)
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: 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 = 17600 nM (pChEMBL 4.75)
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: 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 = 39600 nM (pChEMBL 4.400000095367432)
Descriptors: MW 360.42, ALogP 2.95, HBA 6, HBD 1, PSA 74.66, QED 0.72
Compound (SMILES): NC1=NC2(COC1)c1cc(Br)ccc1OCC21CC1
InChIKey: VDIQADCRFALOMC-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 = 40300 nM (pChEMBL 4.389999866485596)
Descriptors: MW 323.19, ALogP 2.2, HBA 4, HBD 1, PSA 56.84, QED 0.8
Compound (SMILES): NC1=NC2(COC1)c1cc(-c3cncnc3)ccc1OCC21CC1
InChIKey: AMQPJZMLPSZGED-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 = 1210 nM (pChEMBL 5.920000076293945)
Descriptors: MW 322.37, ALogP 1.9, HBA 6, HBD 1, PSA 82.62, QED 0.87
Compound (SMILES): NC1=NC2(c3cc(Br)ccc3OCC23CC3)C(F)(F)CO1
InChIKey: IZCQKTPKYGLDEA-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 = 55800 nM (pChEMBL 4.25)
Descriptors: MW 359.17, ALogP 2.8, HBA 4, HBD 1, PSA 56.84, QED 0.78
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: Ki = 10.3 nM (pChEMBL 7.989999771118164)
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: Ki = 10.2 nM (pChEMBL 7.989999771118164)
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: Ki = 42.9 nM (pChEMBL 7.369999885559082)
Descriptors: MW 425.45, ALogP 1.47, HBA 9, HBD 2, PSA 130.18, QED 0.76
Compound (SMILES): CC1(C)Oc2ccc(NC(=O)c3ccc(Cl)cn3)cc2[C@@]2(COC(N)=N2)C12CC2
InChIKey: SUARPGUFOBBSJS-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: Ki = 37.8 nM (pChEMBL 7.420000076293945)
Descriptors: MW 412.88, ALogP 3.48, HBA 6, HBD 2, PSA 98.83, QED 0.79