lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(c1cc(N[C@H]2CCc3ccccc32)ncn1)[C@@H]1C[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]1O
InChIKey: DZYUSVZBAAKQBE-QTAXSFQDSA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8TBC4
Assay: Inhibition of recombinant human NAEalpha/N-terminal His-tagged NAEbeta expressed in baculovirus infected insect Sf9 cells using N-terminal FLAG tagged Nedd8 as substrate incubated for 105 mins in presence of N-terminal GST-tagged Ubc12 by FRET assay
Measurement: IC50 <= 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 449.53, ALogP 0.34, HBA 9, HBD 4, PSA 150.9, QED 0.47
Compound (SMILES): O=C(O)CNc1nc(NCc2ccc(NC(=O)c3ccc(F)cc3)cc2)c2ccccc2n1
InChIKey: SOXJJHASOJTRAT-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 > 22449 nM (pChEMBL 4.64900016784668)
Descriptors: MW 445.45, ALogP 4.13, HBA 6, HBD 4, PSA 116.24, QED 0.32
Compound (SMILES): O=C(COc1cccc2cccnc12)NCC(O)CN1CCc2ccccc2C1
InChIKey: ZVCIZCPAJITPQB-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 391.47, ALogP 2.15, HBA 5, HBD 2, PSA 74.69, QED 0.65
Compound (SMILES): CCc1ccccc1-n1c(Cn2nc(-c3cc(O)cc(F)c3)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: XMBGXEUSSOESCL-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 520.57, ALogP 5.14, HBA 8, HBD 2, PSA 111.85, QED 0.33
Compound (SMILES): NS(=O)(=O)OC[C@@H]1C[C@@H](Nc2ncnc3nc(-c4cccc5cccnc45)[nH]c23)C[C@@H]1O
InChIKey: YJOGNMKCPNNOIL-GUTXKFCHSA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8TBC4
Assay: Inhibition of recombinant human NAEalpha/N-terminal His-tagged NAEbeta expressed in baculovirus infected insect Sf9 cells using N-terminal FLAG tagged Nedd8 as substrate incubated for 105 mins in presence of N-terminal GST-tagged Ubc12 by FRET assay
Measurement: IC50 <= 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 455.5, ALogP 1.34, HBA 9, HBD 4, PSA 169, QED 0.33
Compound (SMILES): OC(COCc1ccccn1)CN1CCc2ccccc2C1
InChIKey: YSGGELQGLZVDRW-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 10001 nM (pChEMBL 5)
Descriptors: MW 298.39, ALogP 2.02, HBA 4, HBD 1, PSA 45.59, QED 0.89
Compound (SMILES): CCC(Nc1ncnc2[nH]cnc12)c1cc2cccc(C)c2c(=O)n1-c1ccc(F)cc1
InChIKey: OSPMBYVOTOOSBW-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 428.47, ALogP 4.67, HBA 6, HBD 2, PSA 88.49, QED 0.42
Compound (SMILES): CC(C)(C)COc1ncnc2[nH]cc(/C=C/C(N)=O)c12
InChIKey: FVFLNMVKWNRXOS-SNAWJCMRSA-N
Target: TAK1/TAB1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O43318
Assay: Inhibition of kinase tracer-236 binding to full length recombinant human His-tagged TAK1-TAB1 expressed in baculovirus by FRET assay
Measurement: IC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 274.32, ALogP 1.88, HBA 4, HBD 2, PSA 93.89, QED 0.83
Compound (SMILES): CN(C)CCOc1ccc(Nc2cc(-n3cnc4ccccc43)ncn2)nc1
InChIKey: CQLFRGIYOHYSJV-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of recombinant full-length human C-terminal His6-tagged CDK2/recombinant full-length human N-terminal GST-tagged cyclin E using fluorescein-QSPKKG-CONH2 as substrate after 60 mins by off-chip mobility shift assay
Measurement: IC50 = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 375.44, ALogP 2.89, HBA 8, HBD 1, PSA 80.99, QED 0.53
Compound (SMILES): Cn1cnc2ccc(-c3cccc(OCC(O)CN4CCc5ccccc5C4CC(N)=O)c3)cc21
InChIKey: WHFJLNJNRGTUTD-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 470.57, ALogP 3.45, HBA 6, HBD 2, PSA 93.61, QED 0.41
Compound (SMILES): Cc1ccccc1-n1c(Cn2nc(-c3cn[nH]c3)c3c(N)ncnc32)cc2ccccc2c1=O
InChIKey: PGWINMDSIFCGOA-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110delta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 448.49, ALogP 3.46, HBA 8, HBD 2, PSA 120.3, QED 0.43
Compound (SMILES): COCc1nn(Cc2cc3cccc(C)c3c(=O)n2-c2ccccc2C)c2ncnc(N)c12
InChIKey: VYDGDFMNTBRXEJ-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110delta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 440.51, ALogP 3.52, HBA 8, HBD 1, PSA 100.85, QED 0.45
Compound (SMILES): CCNC(=O)/C=C/c1c[nH]c2ncnc(OCC(C)C)c12
InChIKey: SUSVWEQZHZXFBT-AATRIKPKSA-N
Target: TAK1/TAB1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O43318
Assay: Inhibition of kinase tracer-236 binding to full length recombinant human His-tagged TAK1-TAB1 expressed in baculovirus by FRET assay
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 288.35, ALogP 2.14, HBA 4, HBD 2, PSA 79.9, QED 0.8
Compound (SMILES): C[C@H](Nc1ncnc(N)c1C#N)c1nn2cc(F)cc2c(=O)n1-c1ccccc1
InChIKey: RWKKPQPNWMOUQT-NSHDSACASA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of full length recombinant human N-terminal His6-tagged PI3K p110delta/human p85alpha expressed in baculovirus infected sf21 cells using PIP2 as substrate preincubated for 30 mins followed by substrate addition by HTRF assay
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 390.38, ALogP 2.04, HBA 9, HBD 2, PSA 126.92, QED 0.55
Compound (SMILES): CC(C)COc1ncnc2[nH]cc(/C=C/C(=O)N(C)C)c12
InChIKey: OMSUAZHPXSYOQO-AATRIKPKSA-N
Target: TAK1/TAB1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O43318
Assay: Inhibition of kinase tracer-236 binding to full length recombinant human His-tagged TAK1-TAB1 expressed in baculovirus by FRET assay
Measurement: IC50 = 97 nM (pChEMBL 7.010000228881836)
Descriptors: MW 288.35, ALogP 2.09, HBA 4, HBD 1, PSA 71.11, QED 0.86
Compound (SMILES): Cc1cccc2cc(Cn3nc(Br)c4c(N)ncnc43)n(-c3ccccc3F)c(=O)c12
InChIKey: ANJIVPIBXYRVPE-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 479.31, ALogP 3.97, HBA 7, HBD 1, PSA 91.62, QED 0.42
Compound (SMILES): CNC(=O)Cn1ccc2cnc(-c3ccnc(NCC(O)CN4CCc5ccccc5C4)c3)nc21
InChIKey: VJSRWTBVRULRJW-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 471.57, ALogP 2.07, HBA 8, HBD 3, PSA 108.2, QED 0.36
Compound (SMILES): Cc1nnc2ccc(C(=O)N3CCC[C@H]3c3ccc(Cl)cc3)cn12
InChIKey: UJIAQMCWYMQXCS-INIZCTEOSA-N
Target: CDK8/Cyclin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P49336
Assay: Inhibition of Alexa647 tracer binding to full length recombinant human His-tagged CDK8/cyclin C expressed in Baculovirus expression system preincubated for 20 mins followed by tracer addition and incubated in dark for 60 mins by FRET-based Lanthascreen assay
Measurement: IC50 = 3990 nM (pChEMBL 5.400000095367432)
Descriptors: MW 340.81, ALogP 3.67, HBA 4, HBD 0, PSA 50.5, QED 0.71
Compound (SMILES): CN(Cc1ccccc1)c1nccc(N[C@@H]2C[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]2O)n1
InChIKey: GAGSMPCZAKUZKK-SRABZTEZSA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8TBC4
Assay: Inhibition of recombinant human NAEalpha/N-terminal His-tagged NAEbeta expressed in baculovirus infected insect Sf9 cells using N-terminal FLAG tagged Nedd8 as substrate incubated for 105 mins in presence of N-terminal GST-tagged Ubc12 by FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 423.5, ALogP -0.14, HBA 9, HBD 4, PSA 150.9, QED 0.45
Compound (SMILES): O=C(COc1c(CN2CCOCC2)ccc2cccnc12)NC[C@H](O)CN1CCc2ccccc2C1
InChIKey: IWYOGMGHJHUMGH-VWLOTQADSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 490.6, ALogP 1.98, HBA 7, HBD 2, PSA 87.16, QED 0.47
Compound (SMILES): COCCc1cc(O)ccc1-c1ccc2c(-c3nc4ccccc4[nH]3)n[nH]c2c1
InChIKey: KJJMNVMUDVNVSU-UHFFFAOYSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human CDK2 expressed in baculovirus infected Sf9 insect cells/full length recombinant truncated cyclin A expressed in Escherichia coli using retinoblastoma (386 to 928 residues) as substrate after 20 mins by [32P]ATP based scintillation counting analysis
Measurement: Ki = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 384.44, ALogP 4.67, HBA 4, HBD 3, PSA 86.82, QED 0.41
Compound (SMILES): COc1cc(Cl)cc(-c2cccc(OCC(O)CN3CCc4ccccc4C3)c2)c1
InChIKey: RMPINAGEJHZXRP-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 101 nM (pChEMBL 7)
Descriptors: MW 423.94, ALogP 4.81, HBA 4, HBD 1, PSA 41.93, QED 0.59
Compound (SMILES): CC(C)C[C@H]1CNC(=O)c2cc3c[nH]/c(=N/c4ccc(N5CCNCC5)cn4)nc3n21
InChIKey: JQBISHBIDUIUDU-KRWDZBQOSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Kinase Enzymatic Assay: Kinase enzymatic reactions were performed in 384-well microplates using a 12-channel Caliper LabChip instrument as a detection device. The enzymatic phosphorylation of a peptide results in a change in net charge, enabling electrophoretic separation of product from substrate. As substrate and product are separated, two peaks of fluorescence are observed. Change in the relative fluorescence intensity of the substrate and product peaks is the parameter measured, reflecting enzyme activity. In the presence of an inhibitor, the ratio between product and substrate is altered. The signal of the product decreases, while the signal of the substrate increases.For the measurement of CDK2/cyclinE activity, enzyme (0.22 nM) was incubated with 100 mM ATP and the phosphoacceptor substrate peptide (1 mM) for one hour. For the measurement of CDK4/CyclinD activity, enzyme (0.85 nM) was incubated with 200 mM ATP and the phosphoacceptor substrate peptide (1 mM) for three hours. Potential inhibitor compounds (as HCl salts) were tested using 12-point dose response curves in single point at the Km for ATP.
Measurement: IC50 = 50500 nM (pChEMBL 4.300000190734863)
Descriptors: MW 420.52, ALogP 1.73, HBA 7, HBD 3, PSA 103.23, QED 0.6
Compound (SMILES): OC(COC1Cc2ccccc2C1)CN1CCc2ccccc2C1
InChIKey: QRGYSSLCZFORLE-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 1001 nM (pChEMBL 6)
Descriptors: MW 323.44, ALogP 2.59, HBA 3, HBD 1, PSA 32.7, QED 0.92
Compound (SMILES): C[C@H](Nc1nc(N)nc(N)n1)c1nn2cccc2c(=O)n1-c1ccccc1
InChIKey: DFNHVHOQRFJTRN-JTQLQIEISA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of full length recombinant human N-terminal His6-tagged PI3K p110delta/human p85alpha expressed in baculovirus infected sf21 cells using PIP2 as substrate preincubated for 30 mins followed by substrate addition by HTRF assay
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 363.39, ALogP 1.01, HBA 10, HBD 3, PSA 142.04, QED 0.49
Compound (SMILES): Cc1ccccc1-n1c(Cn2nc(C#CCO)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: DIZNSMNZOQAXRV-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110beta/untagged recombinant full length p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 450.5, ALogP 2.72, HBA 8, HBD 2, PSA 111.85, QED 0.41
Compound (SMILES): Cc1ccc2c(NCc3ccc(NC(=O)C4CCN(Cc5ccncc5)CC4)cc3)nc(N(C)C)nc2c1
InChIKey: DLOBJTOTFRGFMG-UHFFFAOYSA-N
Target: TCF4/beta-catenin (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NQB0
Assay: Inhibition of TCF-4/beta catenin in human Tcf33.13 cells expressing Tcf-4/SV40 binding sites driving firefly luciferase reporter gene after 24 hrs by luminometer
Measurement: IC50 = 906 nM (pChEMBL 6.039999961853027)
Descriptors: MW 509.66, ALogP 4.86, HBA 7, HBD 2, PSA 86.28, QED 0.35
Compound (SMILES): Cc1c(Br)c(=O)n(C2CCCC2)c2nc(Nc3ccc(N4CC(C)NC(C)C4)cc3)ncc12
InChIKey: FXOVUUDTLMIHKT-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P11802
Assay: Inhibition of Cdk4/Cyclin D (unknown origin) using retinoblastoma protein substrate and [gamma32P]ATP incubated for 15 mins by beta plate counter based assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 511.47, ALogP 4.91, HBA 7, HBD 2, PSA 75.08, QED 0.52
Compound (SMILES): Cc1ccccc1-n1c(Cn2nc(-c3ccc4nc(N)sc4c3)c3c(N)ncnc32)cc2cccc(C)c2c1=O
InChIKey: FHXVEMGLXJPKKI-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human p110alpha/untagged recombinant full length human p85alpha expressed in baculovirus infected Sf21 cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 544.64, ALogP 5.24, HBA 10, HBD 2, PSA 130.53, QED 0.31
Compound (SMILES): CC(C)(C)OC(=O)Nc1cccc(C(=O)NCC(O)CN2Cc3ccccc3C2)c1
InChIKey: XYRWENGTIKXFBB-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 101 nM (pChEMBL 7)
Descriptors: MW 411.5, ALogP 3.14, HBA 5, HBD 3, PSA 90.9, QED 0.68
Compound (SMILES): OC(COc1cccc(-c2ccc3nn[nH]c3c2)c1)CN1CCc2ccccc2C1
InChIKey: UQEWITMMOKCINM-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 101 nM (pChEMBL 7)
Descriptors: MW 400.48, ALogP 3.42, HBA 5, HBD 2, PSA 74.27, QED 0.52
Compound (SMILES): N[C@@H](C(=O)NC[C@@H](O)CN1CCc2ccccc2C1)c1ccccc1
InChIKey: IZNUUHDRNKARPZ-RTBURBONSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 1001 nM (pChEMBL 6)
Descriptors: MW 339.44, ALogP 1.22, HBA 4, HBD 3, PSA 78.59, QED 0.74
Compound (SMILES): O[C@@H](COc1cccc(-c2cccc3cccnc23)c1)CN1CCc2ccccc2C1
InChIKey: ARGAUQJHHDVCOA-XMMPIXPASA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 410.52, ALogP 4.7, HBA 4, HBD 1, PSA 45.59, QED 0.5
Compound (SMILES): O=C(O)c1c[nH]c2cc(Cl)c(-c3ccc(CO)cc3)cc12
InChIKey: NOGWJYQSYBAMTO-UHFFFAOYSA-N
Target: AMP-activated protein kinase (AMPK) alpha-1/beta-1/gamma-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y478
Assay: Activation of recombinant human AMPK alpha1/beta1/gamma1 using Cy5-labelled SAMS as substrate assessed as protection from Thr172 residue dephosphorylation preincubated for 15 mins followed by incubation with PP2a for 60 mins measured 60 mins post okadaic acid/Cy5-labelled SAMS and ATP addition by TR-FRET assay
Measurement: EC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 301.73, ALogP 3.68, HBA 2, HBD 3, PSA 73.32, QED 0.69
Compound (SMILES): COC(=O)N[C@H](C(=O)NCCCC[C@H](C(N)=O)N(CC(C)C)S(=O)(=O)c1ccc(N)cc1)C(c1ccccc1)c1ccccc1
InChIKey: MHWPVVNPUFZBSG-DGPALRBDSA-N
Target: Protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q9YQ12
Assay: Enzymatic Assay : This is a fluorometric assay based on the cleavage by protease of a substrate carrying a donor group (EDANS) and an acceptor group (DABCYL) on each side of the cleavage site, interacting together through fluorescence resonance energy transfer (FRET) as described by Matayoshi et al. (Science 247:954-954, 1990).
Measurement: IC50 = 0.507 nM (pChEMBL 9.289999961853027)
Descriptors: MW 637.8, ALogP 3.61, HBA 7, HBD 4, PSA 173.92, QED 0.14
Compound (SMILES): C[C@]1(c2cc(NC3CCc4cc(Cl)cnc43)ccc2F)N=C(N)COC[C@@H]1F
InChIKey: LLVAUXCCVYNQFH-KKOVZHJLSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 406.86, ALogP 3.91, HBA 5, HBD 2, PSA 72.53, QED 0.81
Compound (SMILES): C[C@]1(c2cc(NCc3nn(C(F)F)cc3Cl)ccc2F)N=C(N)COC[C@@H]1F
InChIKey: RZXYOIJGPYTNGY-WMLDXEAASA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 419.81, ALogP 3.62, HBA 6, HBD 2, PSA 77.46, QED 0.73
Compound (SMILES): C[C@]1(c2cc(NC3CCOC3)ccc2F)N=C(N)COC[C@@H]1F
InChIKey: UPNYTQSKKDHJPL-TWZNPMNKSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 325.36, ALogP 1.97, HBA 5, HBD 2, PSA 68.87, QED 0.89
Compound (SMILES): C[C@]1(c2cc(NC3CCCOC3)ccc2F)N=C(N)COC[C@@H]1F
InChIKey: JPKWXEFYYHRRRJ-BRCNOLGNSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 339.39, ALogP 2.36, HBA 5, HBD 2, PSA 68.87, QED 0.89
Compound (SMILES): C[C@]1(c2cc(NC3CCOCC3)ccc2F)N=C(N)COC[C@@H]1F
InChIKey: AOUYERQDQWXFRI-DOTOQJQBSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 1480 nM (pChEMBL 5.829999923706055)
Descriptors: MW 339.39, ALogP 2.36, HBA 5, HBD 2, PSA 68.87, QED 0.89
Compound (SMILES): C[C@]1(c2cc(NCc3nn(C(F)F)cc3Cl)ccc2F)N=C(N)COCC1(F)F
InChIKey: JQFSKBFJRFOZRE-MRXNPFEDSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 437.8, ALogP 3.92, HBA 6, HBD 2, PSA 77.46, QED 0.7
Compound (SMILES): CC[C@]1(c2cc(NCc3nn(C(F)F)cc3Cl)ccc2F)N=C(N)COCC1(F)F
InChIKey: NUVPFLZJJVXOTE-QGZVFWFLSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 451.83, ALogP 4.31, HBA 6, HBD 2, PSA 77.46, QED 0.64
Compound (SMILES): C[C@]1(c2cc(N[C@H]3CCc4cc(Cl)cnc43)ccc2F)N=C(N)COCC1(F)F
InChIKey: MRMHPBKPLSGSSO-QFBILLFUSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 424.85, ALogP 4.21, HBA 5, HBD 2, PSA 72.53, QED 0.77
Compound (SMILES): C[C@]1(c2cc(Nc3ccc(C#N)cc3)ccc2F)N=C(N)COCC1(F)F
InChIKey: LBGFFZGJEKCFTP-GOSISDBHSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 374.37, ALogP 3.68, HBA 5, HBD 2, PSA 83.43, QED 0.86
Compound (SMILES): CC1(C)OCC(N)=N[C@](C)(c2cc(N[C@H]3CCc4cc(C#N)cnc43)ccc2F)C1(F)F
InChIKey: JAWQNPDVHXPUOL-PGRDOPGGSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 443.47, ALogP 4.21, HBA 6, HBD 2, PSA 96.32, QED 0.74
Compound (SMILES): CC1(C)OCC(N)=N[C@](C)(c2cc(N[C@@H]3CCc4cc(C#N)cnc43)ccc2F)C1(F)F
InChIKey: JAWQNPDVHXPUOL-XMSQKQJNSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 443.47, ALogP 4.21, HBA 6, HBD 2, PSA 96.32, QED 0.74
Compound (SMILES): CC1(C)OCC(N)=N[C@](C)(c2cc(NC3CCc4cc(Cl)cnc43)ccc2F)C1(F)F
InChIKey: QEQRMWYXLWHPTH-FBLFFUNLSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 452.91, ALogP 4.99, HBA 5, HBD 2, PSA 72.53, QED 0.69
Compound (SMILES): CC1(C)OCC(N)=N[C@](C)(c2cc(NC3COc4cc(Cl)cnc43)ccc2F)C1(F)F
InChIKey: KGAFYWZDTGMPJU-YQYDADCPSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 454.88, ALogP 4.44, HBA 6, HBD 2, PSA 81.76, QED 0.72
Compound (SMILES): CC1(C)OCC(N)=N[C@](C)(c2cc(NC3COc4cc(Cl)ccc43)ccc2F)C1(F)F
InChIKey: ONHMGVGQADMHCB-FBLFFUNLSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 453.89, ALogP 5.04, HBA 5, HBD 2, PSA 68.87, QED 0.68
Compound (SMILES): Cn1ccc(Nc2ccc(F)c([C@@]3(C)N=C(N)COC(C)(C)C3(F)F)c2)n1
InChIKey: QYGFFWAZNLLMIB-QGZVFWFLSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 381.4, ALogP 3.32, HBA 6, HBD 2, PSA 77.46, QED 0.86
Compound (SMILES): CC1(C)OCC(N)=N[C@](C)(c2cc(Nc3ccc(F)cc3)ccc2F)C1(F)F
InChIKey: CFNQAYSORUWKLN-LJQANCHMSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 4160 nM (pChEMBL 5.380000114440918)
Descriptors: MW 395.4, ALogP 4.72, HBA 4, HBD 2, PSA 59.64, QED 0.74
Compound (SMILES): CC1(C)OCC(N)=N[C@](C)(c2cc(N[C@H]3CCc4cc(C#N)cnc43)c(F)cc2F)C1(F)F
InChIKey: ZXPMSLQQIPEYLP-HTAPYJJXSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 461.46, ALogP 4.35, HBA 6, HBD 2, PSA 96.32, QED 0.66
Compound (SMILES): CC1(C)OCC(N)=N[C@](C)(c2cc(Nc3ccc(Cl)nc3)ccc2F)C1(F)F
InChIKey: ZHRCZUUYWIYZLZ-GOSISDBHSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 1770 nM (pChEMBL 5.75)
Descriptors: MW 412.84, ALogP 4.63, HBA 5, HBD 2, PSA 72.53, QED 0.72
Compound (SMILES): CC1(C)OCC(N)=N[C@](C)(c2cc(Nc3cncc(F)c3)ccc2F)C1(F)F
InChIKey: QDHCAUCHZFEKAE-GOSISDBHSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 1360 nM (pChEMBL 5.869999885559082)
Descriptors: MW 396.39, ALogP 4.12, HBA 5, HBD 2, PSA 72.53, QED 0.77
Compound (SMILES): CC1(C)OCC(N)=N[C@](C)(c2cc(Nc3cccnc3)ccc2F)C1(F)F
InChIKey: XOQWCIWXRUAODU-GOSISDBHSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 378.4, ALogP 3.98, HBA 5, HBD 2, PSA 72.53, QED 0.85
Compound (SMILES): CC1(C)OCC(N)=N[C@](C)(c2cc(Nc3cncc(C(F)(F)F)c3)ccc2F)C1(F)F
InChIKey: GDPOMHIELXXKQZ-GOSISDBHSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Immunofluorescence Resonance Energy Transfer (FRET) Assay: The FRET assay was performed essentially as described in Gruninger-Leitch et al., Journal of Biological Chemistry (2002) 277(7) 4687-93 (Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases). In summary, a peptide is designed that is cleaved by the protease. The peptide is labelled with dabcyl at the N terminus and Lucifer Yellow at the C-terminus, such that for an intact peptide the Lucifer Yellow fluorescence is quenched by the dabcyl. When the peptide is cut by BACE2, the quenching is removed and a fluorescent signal is generated. The assay was performed as described in Grueninger et al. 2002 at pH 4.5 using a substrate concentration of 5 μM. A FRET peptide based on the TMEM27 sequence was devised. dabcyl-QTLEFLKIPS-LucY (SEQ ID NO: 1). BACE2 had a high activity against this sequence, which is unrelated to the known APP-based substrates. Conversely, BACE1 had insignificant activity against this peptide.
Measurement: IC50 = 3890 nM (pChEMBL 5.409999847412109)
Descriptors: MW 446.4, ALogP 5, HBA 5, HBD 2, PSA 72.53, QED 0.65