lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCC(CC)(Cc1nc2ccc(OCc3ccn(C)n3)cc2n1Cc1ccc(N2CCC(C(F)(F)F)CC2)cc1)C(=O)O
InChIKey: ANNYOROSXWARRJ-UHFFFAOYSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 μg/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds.
Measurement: Ki = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 597.68, ALogP 6.61, HBA 7, HBD 1, PSA 85.41, QED 0.21
Compound (SMILES): Cc1ccc(COc2ccc3nc([C@@H]4CCCC[C@@H]4C(=O)O)n(Cc4ccc(Br)cc4)c3c2)nc1
InChIKey: RPNGLHUBZFJLRE-RPWUZVMVSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 μg/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds. The reaction is allowed to proceed for two hours after which the plate is read on an Envision plate reader in HTRF mode.
Measurement: Ki = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 534.45, ALogP 6.49, HBA 5, HBD 1, PSA 77.24, QED 0.29
Compound (SMILES): Cc1ccc(COc2ccc3nc([C@H]4CCCC[C@H]4C(=O)O)n(Cc4ccc(Br)cc4)c3c2)nc1
InChIKey: RPNGLHUBZFJLRE-BJKOFHAPSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 μg/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds. The reaction is allowed to proceed for two hours after which the plate is read on an Envision plate reader in HTRF mode.
Measurement: Ki = 830 nM (pChEMBL 6.079999923706055)
Descriptors: MW 534.45, ALogP 6.49, HBA 5, HBD 1, PSA 77.24, QED 0.29
Compound (SMILES): Cc1ccc(COc2ccc3nc([C@@H]4CCCC[C@H]4C(=O)O)n(Cc4ccc(Br)cc4)c3c2)nc1
InChIKey: RPNGLHUBZFJLRE-DNQXCXABSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 μg/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds. The reaction is allowed to proceed for two hours after which the plate is read on an Envision plate reader in HTRF mode.
Measurement: Ki = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 534.45, ALogP 6.49, HBA 5, HBD 1, PSA 77.24, QED 0.29
Compound (SMILES): Cc1ccc(COc2ccc3nc([C@H]4CCCC[C@H]4C(=O)O)n(Cc4ccc(-c5ccc(C(F)(F)F)cc5)cc4)c3c2)nc1
InChIKey: HFHYJUFFDJGTLK-XZWHSSHBSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: FLAP Binding Assay: The assay below is used to test the modulatory activity of compounds against FLAP. Human and mouse FLAP-encoding DNA was amplified by polymerase chain reaction and cloned into pFastBac1 (Invitrogen) with a NH2-terminal 6-His tag for expression in Spodoptera frugiperda (Sf-9) cells. FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 Î¼g/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds. The reaction is allowed to proceed for two hours after which the plate is read on an Envision plate reader in HTRF mode.
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 599.65, ALogP 8.41, HBA 5, HBD 1, PSA 77.24, QED 0.19
Compound (SMILES): Cc1ccc(COc2ccc3nc([C@@H]4CCCC[C@@H]4C(=O)O)n(Cc4ccc(-c5ccc(C(F)(F)F)cc5)cc4)c3c2)nc1
InChIKey: HFHYJUFFDJGTLK-IHLOFXLRSA-N
Target: Arachidonate 5-lipoxygenase-activating protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20292
Assay: Homogeneous Time Resolved Fluorescence Assay: FLAP-containing membranes were prepared as was a FITC-labeled FLAP modulator (3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid). The FLAP binding assay is performed in HTRF format (homogeneous time resolved fluorescence). FLAP-containing membranes (1 μg/well final for human) are incubated in the presence of the HTRF ligand, [5-[({[2-(2-{3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropanoyl}hydrazino)-2-oxoethyl]sulfanyl}acetyl)amino]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid] (25 nM final), a terbium labeled anti-His tag antibody (0.5 ng/well final, from Cisbio) and compounds. The reaction is allowed to proceed for two hours after which the plate is read on an Envision plate reader in HTRF mode.
Measurement: Ki = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 599.65, ALogP 8.41, HBA 5, HBD 1, PSA 77.24, QED 0.19
Compound (SMILES): O=C(/C=C/c1ccc(O)c(OC(F)(F)F)c1)CC(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1
InChIKey: VYZIRWXDHRZJKK-IJIVKGSJSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 476.33, ALogP 5.15, HBA 6, HBD 2, PSA 93.06, QED 0.31
Compound (SMILES): COC(=O)CCC(C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1)C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1
InChIKey: FLJGQIKXQXUOOL-ZESFLVPWSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 562.42, ALogP 5.33, HBA 8, HBD 2, PSA 119.36, QED 0.16
Compound (SMILES): CC(C)(C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1)C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1
InChIKey: KFHNMCQTVBXTMI-NXZHAISVSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 504.38, ALogP 5.79, HBA 6, HBD 2, PSA 93.06, QED 0.27
Compound (SMILES): COC(=O)CC(C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1)C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1
InChIKey: ARGXCTKNWTYPSI-YPCIICBESA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 548.39, ALogP 4.94, HBA 8, HBD 2, PSA 119.36, QED 0.19
Compound (SMILES): COC(=O)CCCC(C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1)C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1
InChIKey: HGXHHQJRZSSTLC-NXZHAISVSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 576.44, ALogP 5.72, HBA 8, HBD 2, PSA 119.36, QED 0.14
Compound (SMILES): CCOC(=O)CCC(C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1)C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1
InChIKey: ZRUAQHBZEZFBFC-BQYBEJQRSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 576.44, ALogP 5.72, HBA 8, HBD 2, PSA 119.36, QED 0.14
Compound (SMILES): CC(C)(C)OC(=O)CCC(C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1)C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1
InChIKey: OTDWDXZGWKFHDL-LUZURFALSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 604.5, ALogP 6.5, HBA 8, HBD 2, PSA 119.36, QED 0.13
Compound (SMILES): O=C(O)CCC(C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1)C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1
InChIKey: ORMUYMSCWMNXJZ-LWBLAMGCSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 548.39, ALogP 5.24, HBA 7, HBD 3, PSA 130.36, QED 0.2
Compound (SMILES): CCOC(=O)C(C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1)C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1
InChIKey: LJRLKWHMVNZDFX-NXZHAISVSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 548.39, ALogP 4.94, HBA 8, HBD 2, PSA 119.36, QED 0.19
Compound (SMILES): COC(=O)CCC(C(=O)/C=C/c1ccc([O-])c(OC(F)(F)F)c1)C(=O)/C=C/c1ccc([O-])c(OC(F)(F)F)c1.[Na+].[Na+]
InChIKey: WXKIGYASZGAUFD-JTOUFZQQSA-L
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 560 nM (pChEMBL 6.25)
Descriptors: MW 562.42, ALogP 5.33, HBA 8, HBD 2, PSA 119.36, QED 0.16
Compound (SMILES): COCOCCCC(C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1)C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1
InChIKey: JLCWBJXDUOXABQ-KBXRYBNXSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 578.46, ALogP 5.78, HBA 8, HBD 2, PSA 111.52, QED 0.1
Compound (SMILES): CN(C)C(=O)CCC(C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1)C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1
InChIKey: WXWNXKAVQJPBHQ-BQYBEJQRSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 575.46, ALogP 5.24, HBA 7, HBD 2, PSA 113.37, QED 0.21
Compound (SMILES): O=C(/C=C/c1ccc(O)c(OC(F)(F)F)c1)C(CCOCCO)C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1
InChIKey: PCFHLBINEARSEE-IJIVKGSJSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 564.43, ALogP 4.78, HBA 8, HBD 3, PSA 122.52, QED 0.14
Compound (SMILES): COC(=O)COc1ccc(/C=C/C(=O)CC(=O)/C=C/c2ccc(O)c(OC)c2)cc1OC
InChIKey: CXZWYAAYHGFLNL-KBXRYBNXSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 440.45, ALogP 3.22, HBA 8, HBD 1, PSA 108.36, QED 0.32
Compound (SMILES): COc1cc(/C=C/C(=O)CC(=O)/C=C/c2ccc(OCC(=O)O)c(OC)c2)ccc1O
InChIKey: ZUZNBJYTSIDJHS-FCXRPNKRSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 426.42, ALogP 3.13, HBA 7, HBD 2, PSA 119.36, QED 0.42
Compound (SMILES): COc1cc(/C=C/C(=O)CC(=O)/C=C/c2ccc(O)c(C(F)(F)F)c2)ccc1O
InChIKey: ZVURMUCQBPLFJF-YPCIICBESA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 406.36, ALogP 4.38, HBA 5, HBD 2, PSA 83.83, QED 0.53
Compound (SMILES): CNc1ccc(/C=C/C(=O)CC(=O)/C=C/c2ccc(NC)c(C(F)(F)F)c2)cc1C(F)(F)F
InChIKey: MRIUULSHNQYQAD-FCXRPNKRSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 5800 nM (pChEMBL 5.239999771118164)
Descriptors: MW 470.41, ALogP 6.06, HBA 4, HBD 2, PSA 58.2, QED 0.28
Compound (SMILES): COc1cc(/C=C/C(=O)CC(=O)/C=C/c2cncc(C(F)(F)F)c2)ccc1O
InChIKey: ATCIEJDZYUHJFC-BUSIMMOISA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 391.35, ALogP 4.07, HBA 5, HBD 1, PSA 76.49, QED 0.57
Compound (SMILES): COC(=O)CCC(C(=O)/C=C/c1ccc(O)c(C(F)(F)F)c1)C(=O)/C=C/c1ccc(O)c(C(F)(F)F)c1
InChIKey: WJFWXFYQWFTNPX-ZESFLVPWSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 530.42, ALogP 5.57, HBA 6, HBD 2, PSA 100.9, QED 0.19
Compound (SMILES): N#CCCC(C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1)C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1
InChIKey: GHNQTSHLGSCLRB-FCXRPNKRSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 529.39, ALogP 5.68, HBA 7, HBD 2, PSA 116.85, QED 0.23
Compound (SMILES): CC(C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1)C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1
InChIKey: OMIBZTUSMLEQBM-YPCIICBESA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 490.35, ALogP 5.4, HBA 6, HBD 2, PSA 93.06, QED 0.29
Compound (SMILES): COC(=O)CCC(C(=O)/C=C/c1ccc(O)c(OC(F)(F)F)c1)C(=O)/C=C/c1ccco1
InChIKey: GEWHBCNCXGBFPA-GZFKCFCKSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binidng Assay: First, amyloid beta peptides (1-40, Peptide Institute, Minoh-shi, Osaka) were dissolved in a 50 mM phosphate buffer containing 100 mM sodium chloride (pH 7.5) such that the concentration of the amyloid beta peptides was 100 mM, and then the solution was left to stand for 16 hours at 30 C., thereby producing amyloid beta peptide aggregates. To these amyloid beta peptide, amyloid beta peptide aggregates that had been prepared in advance by the same method and sonicated for 30 minutes under 28-45-100 KHz variation were added by a 1/1000 quantity, whereby uniform amyloid beta peptide aggregates were prepared.The amyloid beta peptide aggregates prepared by the above method, thioflavin-T, and a measurement compound were added in a 50 mM phosphate buffer (pH 7.4) such that the final concentrations thereof were 1 uM, 3 uM, and 0.02 to 20 uM, respectively. The resultant solution was cause to react for 30 minutes at 23 C. with the light shielded.
Measurement: IC50 = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 452.38, ALogP 4.32, HBA 7, HBD 1, PSA 103.04, QED 0.33
Compound (SMILES): C/C=C/C1=CC2=C(CO1)C(=O)[C@]1(C)OC(=O)[C@H](C(O)CCCCC)C1C2
InChIKey: GNZJIIUXMNGZCY-FPOQGDMISA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Inhibition Assay: To conduct the assays, the 250 uM monasuspiloin solution was further diluted with 10% DMSO to prepare 25 uM, and 5 uM monasuspiloin samples, and the final concentration of DMSO in the cell culture was 1%.The cell line used in glucocorticoid receptor (GR) assay was human A-549 cells (cultured in Ham's F12K medium (Gibco, USA), 10% FBS), the cell line used in progesterone receptor (PR) assay was human T-47D cells (cultured in RPMI 1640 medium (Gibco, USA), 10% FBS), and the cell line used in estrogen receptor (ER) assay was human MCF7 cells (cultured in MEM medium (Gibco, USA), 10% FBS). The cells in the exponential phase of growth were washed off with 1 ml of 0.05% trypsin, centrifuged and collected in a centrifuge tube. 1x107 cells were resuspended in 270 ul BES medium (5 mM BES in medium) and 8 to 10 ug of plasmid [pMMTV-SEAP plasmid was used for GR and PR (see FIG. 7), and pTA-ERE-SEAP plasmid (Clontech, USA) was used for ER (see FIG. 8)] were also added.
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 360.45, ALogP 3.24, HBA 5, HBD 1, PSA 72.83, QED 0.58
Compound (SMILES): c1ccc(-c2cn3ccnc3nc2-c2ccc(CN3CC(c4nnc(-c5ccccn5)[nH]4)C3)cc2)cc1
InChIKey: QRHLAQBHEIPVFR-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 484.57, ALogP 4.84, HBA 7, HBD 1, PSA 87.89, QED 0.36
Compound (SMILES): Cc1nc2nc(-c3ccc(CN4CC(c5nnc(-c6ccccn6)[nH]5)C4)cc3)c(-c3ccccc3)cn2n1
InChIKey: WPQSUBWPGDLXMJ-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 499.58, ALogP 4.55, HBA 8, HBD 1, PSA 100.78, QED 0.36
Compound (SMILES): Fc1cnc2nc(-c3ccc(CN4CC(c5nnc(-c6ccccn6)[nH]5)C4)cc3)c(-c3ccccc3)cn12
InChIKey: CNHFQNWBIBKKAW-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 502.56, ALogP 4.98, HBA 7, HBD 1, PSA 87.89, QED 0.35
Compound (SMILES): Clc1cnc2nc(-c3ccc(CN4CC(c5nnc(-c6ccccn6)[nH]5)C4)cc3)c(-c3ccccc3)cn12
InChIKey: JGVMJJLMUPHTRV-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 519.01, ALogP 5.5, HBA 7, HBD 1, PSA 87.89, QED 0.31
Compound (SMILES): c1ccc(-c2cn3ccnc3nc2-c2ccc(CN3CCC(c4nc5ccncc5[nH]4)CC3)cc2)cc1
InChIKey: JYDUMJHVIAOWOQ-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 157 nM (pChEMBL 6.800000190734863)
Descriptors: MW 485.6, ALogP 5.71, HBA 6, HBD 1, PSA 75, QED 0.34
Compound (SMILES): CC(=O)N[C@@H](C)c1ccc(O[C@@H]2CCN(c3nc(N4CC[C@H](F)C4)ncc3F)C2)cc1
InChIKey: KGSKHKYWIVHBRC-UCLAIMLFSA-N
Target: Acetyl-CoA carboxylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O00763
Assay: Spectrophotometric 384 Well Assay: Malonyl CoA formation by acetyl CoA carboxylases is stoichometrically linked to the consumption of ATP. ACC2 activity is measured in a NADH-linked kinetic method measuring ADP generated during the ACC reaction using a coupled lactate dehydrogenase/pyruvate kinase reaction.For biological testing, a human ACC2 construct which lacks the 128 amino acids at the N-terminus for increased solubility (nt 385-6966 in Genbank entry AJ575592) is cloned. The protein is then expressed in insect cells using a baculoviral expression system. Protein purification is performed by anion exchange.All compounds are dissolved in dimethyl sulfoxide (DMSO) to a concentration of 10 mM.Assay reactions are then carried out in 384-well plates, with hACC2 in an appropriate dilution and at final assay concentrations (f.c.) of 100 mM Tris (pH 7.5), 10 mM trisodium citrate, 25 mM KHCO3, 10 mM MgCl2, 0.5 mg/ml BSA, 3.75 mM reduced L-glutathione, 15 U/ml lactate dehydrogenase, 0.5 mM phosphoenolpyruvate.
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 431.49, ALogP 3.02, HBA 6, HBD 1, PSA 70.59, QED 0.76
Compound (SMILES): CC(=O)N[C@@H](C)c1ccc(O[C@@H]2CCN(c3nc(N(C)CC(C)O)ncc3Cl)C2)cc1
InChIKey: VAMCVUMEPNWTJZ-DZNRSUDRSA-N
Target: Acetyl-CoA carboxylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O00763
Assay: Spectrophotometric 384 Well Assay: Malonyl CoA formation by acetyl CoA carboxylases is stoichometrically linked to the consumption of ATP. ACC2 activity is measured in a NADH-linked kinetic method measuring ADP generated during the ACC reaction using a coupled lactate dehydrogenase/pyruvate kinase reaction.For biological testing, a human ACC2 construct which lacks the 128 amino acids at the N-terminus for increased solubility (nt 385-6966 in Genbank entry AJ575592) is cloned. The protein is then expressed in insect cells using a baculoviral expression system. Protein purification is performed by anion exchange.All compounds are dissolved in dimethyl sulfoxide (DMSO) to a concentration of 10 mM.Assay reactions are then carried out in 384-well plates, with hACC2 in an appropriate dilution and at final assay concentrations (f.c.) of 100 mM Tris (pH 7.5), 10 mM trisodium citrate, 25 mM KHCO3, 10 mM MgCl2, 0.5 mg/ml BSA, 3.75 mM reduced L-glutathione, 15 U/ml lactate dehydrogenase, 0.5 mM phosphoenolpyruvate.
Measurement: IC50 = 753 nM (pChEMBL 6.119999885559082)
Descriptors: MW 447.97, ALogP 2.8, HBA 7, HBD 2, PSA 90.82, QED 0.64
Compound (SMILES): CC(=O)N[C@@H](C)c1ccc(O[C@@H]2CCN(c3nc(N4CCOC(C)C4)ncc3Cl)C2)cc1
InChIKey: ZCXGBWHZZJHXRE-XGNAPRINSA-N
Target: Acetyl-CoA carboxylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O00763
Assay: Spectrophotometric 384 Well Assay: Malonyl CoA formation by acetyl CoA carboxylases is stoichometrically linked to the consumption of ATP. ACC2 activity is measured in a NADH-linked kinetic method measuring ADP generated during the ACC reaction using a coupled lactate dehydrogenase/pyruvate kinase reaction.For biological testing, a human ACC2 construct which lacks the 128 amino acids at the N-terminus for increased solubility (nt 385-6966 in Genbank entry AJ575592) is cloned. The protein is then expressed in insect cells using a baculoviral expression system. Protein purification is performed by anion exchange.All compounds are dissolved in dimethyl sulfoxide (DMSO) to a concentration of 10 mM.Assay reactions are then carried out in 384-well plates, with hACC2 in an appropriate dilution and at final assay concentrations (f.c.) of 100 mM Tris (pH 7.5), 10 mM trisodium citrate, 25 mM KHCO3, 10 mM MgCl2, 0.5 mg/ml BSA, 3.75 mM reduced L-glutathione, 15 U/ml lactate dehydrogenase, 0.5 mM phosphoenolpyruvate.
Measurement: IC50 = 204 nM (pChEMBL 6.690000057220459)
Descriptors: MW 459.98, ALogP 3.21, HBA 7, HBD 1, PSA 79.82, QED 0.71