lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC1(C)Oc2ccc(-c3cccc(OCC(F)(F)F)c3)cc2C2(COC(N)=N2)C12COC2
InChIKey: UTEFABOYSUEMPY-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 = 1260 nM (pChEMBL 5.900000095367432)
Descriptors: MW 448.44, ALogP 4.02, HBA 6, HBD 1, PSA 75.3, QED 0.77
Compound (SMILES): CCOc1cccc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C(C)(C)O3)c1
InChIKey: NKMRFFYBJGWRSX-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 = 879 nM (pChEMBL 6.059999942779541)
Descriptors: MW 394.47, ALogP 3.48, HBA 6, HBD 1, PSA 75.3, QED 0.86
Compound (SMILES): CCSc1cccc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C(C)(C)O3)c1
InChIKey: HCCGPLVNNLOSEH-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 = 933 nM (pChEMBL 6.03000020980835)
Descriptors: MW 410.54, ALogP 4.19, HBA 6, HBD 1, PSA 66.07, QED 0.77
Compound (SMILES): CC1(C)Oc2ccc(-c3cc(F)cc(Cl)c3)cc2C2(COC(N)=N2)C12COC2
InChIKey: VELBUBIDIGYSLN-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 = 188 nM (pChEMBL 6.730000019073486)
Descriptors: MW 402.85, ALogP 3.87, HBA 5, HBD 1, PSA 66.07, QED 0.79
Compound (SMILES): CC1(C)Oc2ccc(-c3cc(F)cc(F)c3)cc2C2(COC(N)=N2)C12COC2
InChIKey: GXWZNDMKCKULNS-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 = 621 nM (pChEMBL 6.210000038146973)
Descriptors: MW 386.4, ALogP 3.36, HBA 5, HBD 1, PSA 66.07, QED 0.82
Compound (SMILES): Cc1cc(F)cc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C(C)(C)O3)c1
InChIKey: MHGCEQNGZDTCOC-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 = 614 nM (pChEMBL 6.210000038146973)
Descriptors: MW 382.44, ALogP 3.53, HBA 5, HBD 1, PSA 66.07, QED 0.82
Compound (SMILES): CC1(C)Oc2ccc(-c3cc(F)ccn3)cc2C2(COC(N)=N2)C12COC2
InChIKey: UNACISPQELMJNE-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 = 1593 nM (pChEMBL 5.800000190734863)
Descriptors: MW 369.4, ALogP 2.62, HBA 6, HBD 1, PSA 78.96, QED 0.84
Compound (SMILES): CC1(C)Oc2ccc(-c3cncc(Cl)n3)cc2C2(COC(N)=N2)C12COC2
InChIKey: ZRRKOIHRTBFWMQ-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 = 759 nM (pChEMBL 6.119999885559082)
Descriptors: MW 386.84, ALogP 2.52, HBA 7, HBD 1, PSA 91.85, QED 0.81
Compound (SMILES): Cc1cnc(Cl)c(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C(C)(C)O3)c1
InChIKey: IEPVAYLEYUWVFH-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 = 1360 nM (pChEMBL 5.869999885559082)
Descriptors: MW 399.88, ALogP 3.44, HBA 6, HBD 1, PSA 78.96, QED 0.74
Compound (SMILES): CC1(C)Oc2ccc(-c3cc(Cl)cnc3Cl)cc2C2(COC(N)=N2)C12COC2
InChIKey: HCRMCIFUVDVQDP-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 = 688 nM (pChEMBL 6.159999847412109)
Descriptors: MW 420.3, ALogP 3.78, HBA 6, HBD 1, PSA 78.96, QED 0.71
Compound (SMILES): CC1(C)Oc2ccc(-c3cc(F)cnc3Cl)cc2C2(COC(N)=N2)C12COC2
InChIKey: NXVWQPVBYKAMTH-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 = 1130 nM (pChEMBL 5.949999809265137)
Descriptors: MW 403.84, ALogP 3.27, HBA 6, HBD 1, PSA 78.96, QED 0.74
Compound (SMILES): CC1(C)Oc2ccc(-c3cc(Cl)cnc3F)cc2C2(COC(N)=N2)C12COC2
InChIKey: GETMSLAWJGDJFJ-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 = 313 nM (pChEMBL 6.5)
Descriptors: MW 403.84, ALogP 3.27, HBA 6, HBD 1, PSA 78.96, QED 0.74
Compound (SMILES): COc1ncc(Cl)cc1-c1ccc2c(c1)C1(COC(N)=N1)C1(COC1)C(C)(C)O2
InChIKey: SBSSYSBKPBOHJP-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 = 786 nM (pChEMBL 6.110000133514404)
Descriptors: MW 415.88, ALogP 3.14, HBA 7, HBD 1, PSA 88.19, QED 0.81
Compound (SMILES): CC1(C)Oc2ccc(-c3cccnc3Cl)cc2C2(COC(N)=N2)C12COC2
InChIKey: JMVWCLLKZHGJJD-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 = 2610 nM (pChEMBL 5.579999923706055)
Descriptors: MW 385.85, ALogP 3.13, HBA 6, HBD 1, PSA 78.96, QED 0.76
Compound (SMILES): Cc1cc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C(C)(C)O3)cnc1F
InChIKey: GHRVXMFUXOXBGC-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 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 383.42, ALogP 2.92, HBA 6, HBD 1, PSA 78.96, QED 0.77
Compound (SMILES): CC1(C)Oc2ccc(-c3cc(F)ncc3Cl)cc2C2(COC(N)=N2)C12COC2
InChIKey: OGBRXVOOYQIKKV-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 = 930 nM (pChEMBL 6.03000020980835)
Descriptors: MW 403.84, ALogP 3.27, HBA 6, HBD 1, PSA 78.96, QED 0.74
Compound (SMILES): CC1(C)Oc2ccc(-c3ccnc(Cl)c3Cl)cc2C2(COC(N)=N2)C12COC2
InChIKey: SEAPOZKSVDOWPZ-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 = 2120 nM (pChEMBL 5.670000076293945)
Descriptors: MW 420.3, ALogP 3.78, HBA 6, HBD 1, PSA 78.96, QED 0.71
Compound (SMILES): CC1(C)Oc2ccc(-c3cncc(C#N)c3)cc2C2(COC(N)=N2)C12COC2
InChIKey: LXZVBTDOKAHNDX-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 = 981 nM (pChEMBL 6.010000228881836)
Descriptors: MW 376.42, ALogP 2.35, HBA 7, HBD 1, PSA 102.75, QED 0.82
Compound (SMILES): COc1cc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C(C)(C)O3)c(F)cn1
InChIKey: FAPBBHHBSSJFBQ-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 = 1410 nM (pChEMBL 5.849999904632568)
Descriptors: MW 399.42, ALogP 2.62, HBA 7, HBD 1, PSA 88.19, QED 0.84
Compound (SMILES): COc1cc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C(C)(C)O3)c(Cl)cn1
InChIKey: AHFYJIKDCBGBJZ-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 415.88, ALogP 3.14, HBA 7, HBD 1, PSA 88.19, QED 0.81
Compound (SMILES): CC1(C)Oc2ccc(-c3ccnc(Cl)c3)cc2C2(COC(N)=N2)C12COC2
InChIKey: WMXJIIQTWLMWSN-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 = 1064 nM (pChEMBL 5.96999979019165)
Descriptors: MW 385.85, ALogP 3.13, HBA 6, HBD 1, PSA 78.96, QED 0.76
Compound (SMILES): COc1cc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C(C)(C)O3)ccn1
InChIKey: KHXXKWQBUJEQDU-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 = 2314 nM (pChEMBL 5.639999866485596)
Descriptors: MW 381.43, ALogP 2.48, HBA 7, HBD 1, PSA 88.19, QED 0.86
Compound (SMILES): CC1(C)Oc2ccc(C3=CCCCCC3)cc2C2(COC(N)=N2)C12COC2
InChIKey: YNAMZKYOBIDWHW-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 = 760 nM (pChEMBL 6.119999885559082)
Descriptors: MW 368.48, ALogP 3.76, HBA 5, HBD 1, PSA 66.07, QED 0.82
Compound (SMILES): CC1CC=C(c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C(C)(C)O3)CC1
InChIKey: PQKQEKLALZXTJD-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 = 3630 nM (pChEMBL 5.440000057220459)
Descriptors: MW 368.48, ALogP 3.62, HBA 5, HBD 1, PSA 66.07, QED 0.82
Compound (SMILES): CCC/C=C/c1ccc2c(c1)C1(COC(N)=N1)C1(COC1)C(C)(C)O2
InChIKey: DKGSWKREOJWJTP-VOTSOKGWSA-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 = 869 nM (pChEMBL 6.059999942779541)
Descriptors: MW 342.44, ALogP 3.23, HBA 5, HBD 1, PSA 66.07, QED 0.92
Compound (SMILES): CC1(C)Oc2ccc(-c3cnc4[nH]ccc4c3)cc2C2(COC(N)=N2)C12COC2
InChIKey: FIXVOAGHXZBUQU-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 = 760 nM (pChEMBL 6.119999885559082)
Descriptors: MW 390.44, ALogP 2.96, HBA 6, HBD 2, PSA 94.75, QED 0.67
Compound (SMILES): CC1(C)Oc2ccc(-c3cc(O)cc(F)c3)cc2C2(COC(N)=N2)C12COC2
InChIKey: XLOPHQHRSBOSNE-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 = 1410 nM (pChEMBL 5.849999904632568)
Descriptors: MW 384.41, ALogP 2.93, HBA 6, HBD 2, PSA 86.3, QED 0.79
Compound (SMILES): CC1(C)Oc2ccc(-c3cc(C#N)ccc3F)cc2C2(COC(N)=N2)C12COC2
InChIKey: GSTHBYLKRBWKOI-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 = 1000 nM (pChEMBL 6)
Descriptors: MW 393.42, ALogP 3.09, HBA 6, HBD 1, PSA 89.86, QED 0.8
Compound (SMILES): CNC(=O)c1cc(F)cc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C(C)(C)O3)c1
InChIKey: UQPAONODJFHYMD-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 = 2240 nM (pChEMBL 5.650000095367432)
Descriptors: MW 425.46, ALogP 2.58, HBA 6, HBD 2, PSA 95.17, QED 0.77
Compound (SMILES): CCC1CC=C(c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)C(C)(C)O3)CC1
InChIKey: CTBXKHLRFQFYGO-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 = 2240 nM (pChEMBL 5.650000095367432)
Descriptors: MW 382.5, ALogP 4.01, HBA 5, HBD 1, PSA 66.07, QED 0.84
Compound (SMILES): CC1(C)Oc2ccc(-c3cncc(Cl)c3)cc2C2(COC(N)=N2)C12COC2
InChIKey: SVHNMBSDZDNXOE-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 = 401 nM (pChEMBL 6.400000095367432)
Descriptors: MW 385.85, ALogP 3.13, HBA 6, HBD 1, PSA 78.96, QED 0.82
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: 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 = 3350 nM (pChEMBL 5.46999979019165)
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: 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 = 3230 nM (pChEMBL 5.489999771118164)
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: 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 = 994 nM (pChEMBL 6)
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: 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 = 2120 nM (pChEMBL 5.670000076293945)
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: 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 = 1150 nM (pChEMBL 5.940000057220459)
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: 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 = 3240 nM (pChEMBL 5.489999771118164)
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: 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 = 2030 nM (pChEMBL 5.690000057220459)
Descriptors: MW 401.47, ALogP 3.63, HBA 6, HBD 1, PSA 78.96, QED 0.67