lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Nc1ccc(-c2cncc([C@H]3C[C@H]4CC[C@H]3N4)c2)cn1
InChIKey: ZFGBGFZJMOWQLH-RBSFLKMASA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P09483
Assay: Displacement of [3H]-epibatidine from alpha4beta2 nAChR in rat cerebral cortex homogenates after 4 hrs by liquid scintillation counting
Measurement: Ki = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 266.35, ALogP 2.33, HBA 4, HBD 2, PSA 63.83, QED 0.88
Compound (SMILES): COc1ccc(-c2cncc([C@H]3C[C@H]4CC[C@H]3N4)c2)cn1
InChIKey: MTXSKMIYEOQGMK-BZUAXINKSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P09483
Assay: Displacement of [3H]-epibatidine from alpha4beta2 nAChR in rat cerebral cortex homogenates after 4 hrs by liquid scintillation counting
Measurement: Ki = 0.27 nM (pChEMBL 9.569999694824219)
Descriptors: MW 281.36, ALogP 2.76, HBA 4, HBD 1, PSA 47.04, QED 0.94
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CCCNC2=O
InChIKey: ZNLXCLMQEIQSAS-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type ALK (unknown origin) by homogeneous time resolved fluorescence assay
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 516.02, ALogP 4.48, HBA 8, HBD 3, PSA 122.31, QED 0.42
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)C(=O)NCCC2
InChIKey: HQHWKSPSJJCZPM-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 516.02, ALogP 4.48, HBA 8, HBD 3, PSA 122.31, QED 0.42
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CCNC(=O)C2
InChIKey: OIPVNLQCUGTYJW-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type ALK (unknown origin) by homogeneous time resolved fluorescence assay
Measurement: IC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 516.02, ALogP 4.02, HBA 8, HBD 3, PSA 122.31, QED 0.43
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CCCNC2
InChIKey: MMJWRPJCZSSSNA-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 502.04, ALogP 4.84, HBA 8, HBD 3, PSA 105.24, QED 0.42
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CNCCC2
InChIKey: CENVUXSKJJMKIU-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 502.04, ALogP 4.84, HBA 8, HBD 3, PSA 105.24, QED 0.42
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CCNCC2
InChIKey: IXPKKOYDMRELAG-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type ALK (unknown origin) by homogeneous time resolved fluorescence assay
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 502.04, ALogP 4.5, HBA 8, HBD 3, PSA 105.24, QED 0.43
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CNCCO2
InChIKey: QDJZMRPVQLAGDJ-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type ALK (unknown origin) by homogeneous time resolved fluorescence assay
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 504.01, ALogP 4.29, HBA 9, HBD 3, PSA 114.47, QED 0.43
Compound (SMILES): CCN1CCCc2cc(Nc3ncc(Cl)c(Nc4ccccc4S(=O)(=O)C(C)C)n3)c(OC)cc2C1
InChIKey: LXPOMXGDVJAVRC-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type ALK (unknown origin) by homogeneous time resolved fluorescence assay
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 530.09, ALogP 5.58, HBA 8, HBD 2, PSA 96.45, QED 0.39
Compound (SMILES): CCN1CCCc2cc(OC)c(Nc3ncc(Cl)c(Nc4ccccc4S(=O)(=O)C(C)C)n3)cc2C1
InChIKey: GYKCLKQWDUOGKZ-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 530.09, ALogP 5.58, HBA 8, HBD 2, PSA 96.45, QED 0.39
Compound (SMILES): CCN1CCc2cc(Nc3ncc(Cl)c(Nc4ccccc4S(=O)(=O)C(C)C)n3)c(OC)cc2CC1
InChIKey: HULMBKWINBUXAH-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type ALK (unknown origin) by homogeneous time resolved fluorescence assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 530.09, ALogP 5.23, HBA 8, HBD 2, PSA 96.45, QED 0.41
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CCCN(C(C)=O)C2
InChIKey: CPQPQASNGAKBFB-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 544.08, ALogP 5.1, HBA 8, HBD 2, PSA 113.52, QED 0.42
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CN(C(C)=O)CCC2
InChIKey: QRYAORAAWVXYEL-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 544.08, ALogP 5.1, HBA 8, HBD 2, PSA 113.52, QED 0.42
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CCCN(C(=O)CO)C2
InChIKey: XEYNCJLHGRIWJF-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type ALK (unknown origin) by homogeneous time resolved fluorescence assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 560.08, ALogP 4.08, HBA 9, HBD 3, PSA 133.75, QED 0.37
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CN(C(=O)CO)CCC2
InChIKey: XYPDMOWNWKTDJZ-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 560.08, ALogP 4.08, HBA 9, HBD 3, PSA 133.75, QED 0.37
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CCN(C(=O)CO)CC2
InChIKey: GYUJZBRIDJQKEL-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 560.08, ALogP 3.73, HBA 9, HBD 3, PSA 133.75, QED 0.38
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CCCN(CCO)C2
InChIKey: XJWNNWKYALKNDK-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 546.09, ALogP 4.55, HBA 9, HBD 3, PSA 116.68, QED 0.36
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CN(CCO)CCC2
InChIKey: IRMGIUINRNWTRL-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type ALK (unknown origin) by homogeneous time resolved fluorescence assay
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 546.09, ALogP 4.55, HBA 9, HBD 3, PSA 116.68, QED 0.36
Compound (SMILES): Cn1cnc(-c2cc3nccc(Oc4ccc(NC(=O)c5cnn(-c6ccccc6)c5-c5ccccc5)cc4F)c3s2)c1
InChIKey: LVVUVXCYFVJIIX-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met phosphorylation in human MKN45 cells
Measurement: IC50 = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 586.65, ALogP 7.73, HBA 8, HBD 1, PSA 86.86, QED 0.21
Compound (SMILES): Cn1cnc(-c2cc3nccc(Oc4ccc(NC(=O)c5cn(-c6ccccc6)nc5-c5ccccc5)cc4F)c3s2)c1
InChIKey: ZBSTZJARMUEZIU-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met phosphorylation in human MKN45 cells
Measurement: IC50 = 2070 nM (pChEMBL 5.679999828338623)
Descriptors: MW 586.65, ALogP 7.73, HBA 8, HBD 1, PSA 86.86, QED 0.21
Compound (SMILES): Cn1cnc(-c2cc3nccc(Oc4ccc(NC(=O)c5sc(-c6ccccc6)nc5-c5ccccc5)cc4F)c3s2)c1
InChIKey: OXWIOZKINSUAPC-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met phosphorylation in human MKN45 cells
Measurement: IC50 = 2260 nM (pChEMBL 5.650000095367432)
Descriptors: MW 603.7, ALogP 8.67, HBA 8, HBD 1, PSA 81.93, QED 0.2
Compound (SMILES): Cn1cnc(-c2cc3nccc(Oc4ccc(NC(=O)c5cc(-c6ccccc6)n(-c6ccccc6)c5)cc4F)c3s2)c1
InChIKey: KNIRVRLUQOCHFV-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met phosphorylation in human MKN45 cells
Measurement: IC50 = 4840 nM (pChEMBL 5.320000171661377)
Descriptors: MW 585.66, ALogP 8.34, HBA 7, HBD 1, PSA 73.97, QED 0.2
Compound (SMILES): Cn1cnc(-c2cc3nccc(Oc4ccc(NC(=O)c5cnn(-c6ccccc6)c5-c5ccccc5F)cc4F)c3s2)c1
InChIKey: VMIMHFCIAFUSHW-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met phosphorylation in human MKN45 cells
Measurement: IC50 = 1090 nM (pChEMBL 5.960000038146973)
Descriptors: MW 604.64, ALogP 7.87, HBA 8, HBD 1, PSA 86.86, QED 0.2
Compound (SMILES): COc1ccccc1-c1c(C(=O)Nc2ccc(Oc3ccnc4cc(-c5cn(C)cn5)sc34)c(F)c2)cnn1-c1ccccc1
InChIKey: MPKSQOZOHKEBQM-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met phosphorylation in human MKN45 cells
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 616.68, ALogP 7.74, HBA 9, HBD 1, PSA 96.09, QED 0.19
Compound (SMILES): Cn1cnc(-c2cc3nccc(Oc4ccc(NC(=O)c5cnn(-c6ccccc6)c5-c5ccccn5)cc4F)c3s2)c1
InChIKey: WUPSOUMWBFYXSC-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met phosphorylation in human MKN45 cells
Measurement: IC50 = 1230 nM (pChEMBL 5.909999847412109)
Descriptors: MW 587.64, ALogP 7.13, HBA 9, HBD 1, PSA 99.75, QED 0.21
Compound (SMILES): COc1cccc(-c2c(C(=O)Nc3ccc(Oc4ccnc5cc(-c6cn(C)cn6)sc45)c(F)c3)cnn2-c2ccccc2)c1
InChIKey: HBFSOOUBBFCSKA-UHFFFAOYSA-N
Target: Macrophage-stimulating protein receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q04912
Assay: Inhibition of human RON
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 616.68, ALogP 7.74, HBA 9, HBD 1, PSA 96.09, QED 0.19
Compound (SMILES): Cn1cnc(-c2cc3nccc(Oc4ccc(NC(=O)c5cnn(-c6ccccc6)c5-c5cccnc5)cc4F)c3s2)c1
InChIKey: CXWRJKJKIGCZER-UHFFFAOYSA-N
Target: Macrophage-stimulating protein receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q04912
Assay: Inhibition of human RON
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 587.64, ALogP 7.13, HBA 9, HBD 1, PSA 99.75, QED 0.21
Compound (SMILES): Cn1cnc(-c2cc3nccc(Oc4ccc(NC(=O)c5cnn(-c6ccccc6)c5-c5ccc(F)cc5)cc4F)c3s2)c1
InChIKey: GJNFPKYJZXRLHF-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met phosphorylation in human MKN45 cells
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 604.64, ALogP 7.87, HBA 8, HBD 1, PSA 86.86, QED 0.2
Compound (SMILES): CCO[C@H]1OC[C@]23CCC[C@]1(C)[C@@H]2CC[C@]1(C)[C@@H]3CC[C@](C)(O)[C@H]1Cc1cc(O)ccc1O
InChIKey: LWFHXTDIICCALN-PCEGHUARSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin) pre-incubated for 10 mins before addition of p-nitrophenyl phosphate substrate and measured 30 mins post substrate addition
Measurement: IC50 = 8700 nM (pChEMBL 5.059999942779541)
Descriptors: MW 458.64, ALogP 5.4, HBA 5, HBD 3, PSA 79.15, QED 0.53
Compound (SMILES): CO[C@H]1OC[C@]23CCC[C@]1(C)[C@@H]2CC[C@]1(C)[C@@H]3CC[C@]2(C)Oc3ccccc3C[C@@H]12
InChIKey: VYTRYBMUYJDNIN-RGCARSLISA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin) pre-incubated for 10 mins before addition of p-nitrophenyl phosphate substrate and measured 30 mins post substrate addition
Measurement: IC50 = 8500 nM (pChEMBL 5.070000171661377)
Descriptors: MW 410.6, ALogP 6, HBA 3, HBD 0, PSA 27.69, QED 0.57
Compound (SMILES): C[C@]12CCC[C@@]3(CO[C@@H]1O)[C@H]2CC[C@]1(C)[C@@H]3CC[C@]2(C)Oc3ccc(O)cc3C[C@@H]12
InChIKey: CZBILTFRGJCVGE-BGLMPXDFSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin) pre-incubated for 10 mins before addition of p-nitrophenyl phosphate substrate and measured 30 mins post substrate addition
Measurement: IC50 = 11900 nM (pChEMBL 4.920000076293945)
Descriptors: MW 412.57, ALogP 5.05, HBA 4, HBD 2, PSA 58.92, QED 0.63
Compound (SMILES): C[C@]1(CO)CCC[C@@]2(CO)[C@H]1CC[C@]1(C)[C@@H]2CC[C@]2(C)Oc3ccc(O)cc3C[C@@H]12
InChIKey: LLYSRQZRILIUOI-NVDMUHRWSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTP1B (unknown origin) pre-incubated for 10 mins before addition of p-nitrophenyl phosphate substrate and measured 30 mins post substrate addition
Measurement: IC50 = 14800 nM (pChEMBL 4.829999923706055)
Descriptors: MW 414.59, ALogP 4.69, HBA 4, HBD 3, PSA 69.92, QED 0.66
Compound (SMILES): O=C1c2cc(-c3ccnc(N[C@H]4[C@@H]5COC[C@@H]54)n3)cn2CCCN1[C@H](CO)c1cccc(Cl)c1
InChIKey: VWIPLWQZQDSGGV-VNHKHXMHSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of ERK2 (unknown origin)
Measurement: IC50 = 0.026 nM (pChEMBL 10.59000015258789)
Descriptors: MW 479.97, ALogP 3.23, HBA 7, HBD 2, PSA 92.51, QED 0.56
Compound (SMILES): O=C1c2cc(-c3ccnc(NC4CCOCC4)n3)cn2C[C@@H](F)CN1[C@H](CO)c1cccc(Cl)c1
InChIKey: MUDIOFOOIFLHMM-AUSIDOKSSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of ERK2 (unknown origin)
Measurement: IC50 = 0.05 nM (pChEMBL 10.300000190734863)
Descriptors: MW 499.97, ALogP 3.72, HBA 7, HBD 2, PSA 92.51, QED 0.54
Compound (SMILES): O=C1c2cc(-c3ccnc(NC4CCOCC4)n3)cn2CCCN1[C@H](CO)c1cccc(Cl)c1
InChIKey: KQDDJNKQTVYZHY-HSZRJFAPSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of ERK2 (unknown origin)
Measurement: IC50 = 0.01 nM (pChEMBL 11)
Descriptors: MW 481.98, ALogP 3.77, HBA 7, HBD 2, PSA 92.51, QED 0.56
Compound (SMILES): O=C1c2cc(-c3ccnc(NC4CCOCC4)n3)cn2CCCN1[C@H](CO)c1cc(F)cc(Cl)c1
InChIKey: GLQKDONMZPBGGT-HSZRJFAPSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of ERK2 (unknown origin)
Measurement: IC50 = 0.019 nM (pChEMBL 10.720000267028809)
Descriptors: MW 499.97, ALogP 3.91, HBA 7, HBD 2, PSA 92.51, QED 0.53
Compound (SMILES): CC(C)Nc1nccc(-c2cc3n(c2)CCN(Cc2ccccc2)C3=O)n1
InChIKey: DXLFCNCRKRXJJA-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of ERK2 (unknown origin)
Measurement: IC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 361.45, ALogP 3.42, HBA 5, HBD 1, PSA 63.05, QED 0.76
Compound (SMILES): O=C1c2cc(-c3ccnc(NC4CCOCC4)n3)cn2CCN1[C@H](CO)c1cccc(Cl)c1
InChIKey: PJPXAFCTLKCTJP-JOCHJYFZSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Inhibition of ERK2 (unknown origin)
Measurement: IC50 = 0.16 nM (pChEMBL 9.800000190734863)
Descriptors: MW 467.96, ALogP 3.38, HBA 7, HBD 2, PSA 92.51, QED 0.58
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CCN(CCO)CC2
InChIKey: CADNXFFPEKAFHJ-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 546.09, ALogP 4.2, HBA 9, HBD 3, PSA 116.68, QED 0.36
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CCCN(C1CCNCC1)C2
InChIKey: INPHYWINOJFIAJ-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type ALK (unknown origin) by homogeneous time resolved fluorescence assay
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 585.17, ALogP 5.31, HBA 9, HBD 3, PSA 108.48, QED 0.32
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CN(C1CCNCC1)CCC2
InChIKey: NPPASAYBDKHVDT-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type ALK (unknown origin) by homogeneous time resolved fluorescence assay
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 585.17, ALogP 5.31, HBA 9, HBD 3, PSA 108.48, QED 0.32
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CCCN(C1CCOCC1)C2
InChIKey: UCEAVAQSKJVJFP-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 = 0.78 nM (pChEMBL 9.109999656677246)
Descriptors: MW 586.16, ALogP 5.74, HBA 9, HBD 2, PSA 105.68, QED 0.34
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CN(C1CCOCC1)CCC2
InChIKey: DZDHTEOJHDYEPP-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 586.16, ALogP 5.74, HBA 9, HBD 2, PSA 105.68, QED 0.34
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CCCN(C1COC1)C2
InChIKey: WCCLJJOUCIHEBN-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 558.1, ALogP 4.95, HBA 9, HBD 2, PSA 105.68, QED 0.4
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CN(C1COC1)CCC2
InChIKey: WAMHTMOXRWVKNP-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 558.1, ALogP 4.95, HBA 9, HBD 2, PSA 105.68, QED 0.4
Compound (SMILES): Cc1nsc(-c2nnc3n2CCN(C(=O)c2ccc(F)cc2)[C@@H]3C)n1
InChIKey: PPSNFPASKFYPMN-SECBINFHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 90000 nM (pChEMBL 4.050000190734863)
Descriptors: MW 358.4, ALogP 2.46, HBA 7, HBD 0, PSA 76.8, QED 0.7
Compound (SMILES): Cc1nnc(-c2nnc3n2CCN(C(=O)c2ccc(F)cc2)[C@@H]3C)s1
InChIKey: CAIWJHRYFVPEML-SECBINFHSA-N
Target: Neuromedin-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P29371
Assay: Antagonist activity against human recombinant NK3R expressed in CHO cells by aequorin functional assay
Measurement: IC50 = 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 358.4, ALogP 2.46, HBA 7, HBD 0, PSA 76.8, QED 0.7
Compound (SMILES): Cc1noc(-c2nnc3n2CCN(C(=O)c2ccc(F)cc2)[C@@H]3C)n1
InChIKey: MRAPDPPDTOESHB-SECBINFHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 342.33, ALogP 1.99, HBA 7, HBD 0, PSA 89.94, QED 0.71
Compound (SMILES): CC(C)c1noc(-c2nnc3n2CCN(C(=O)c2ccc(F)cc2)[C@@H]3C)n1
InChIKey: VCDLSNHPAIHNNG-LLVKDONJSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 370.39, ALogP 2.81, HBA 7, HBD 0, PSA 89.94, QED 0.7
Compound (SMILES): Cc1nsc(-c2nnc3n2CCN(C(=O)c2ccc(F)cc2)C3)n1
InChIKey: UHNVQJPBRBMNNN-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 344.38, ALogP 1.9, HBA 7, HBD 0, PSA 76.8, QED 0.71
Compound (SMILES): C[C@@H]1c2nnc(-c3ncns3)n2CCN1C(=O)c1ccc(F)cc1
InChIKey: VLHNGOVFBBNFFJ-SECBINFHSA-N
Target: Neuromedin-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P29371
Assay: Antagonist activity against human recombinant NK3R expressed in CHO cells by aequorin functional assay
Measurement: IC50 = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 344.38, ALogP 2.15, HBA 7, HBD 0, PSA 76.8, QED 0.71
Compound (SMILES): Cc1nsc(-c2nnc3n2CCN(C(=O)c2ccc(F)cc2)C3(C)C)n1
InChIKey: CGCSZFVIPKLGCF-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 372.43, ALogP 2.64, HBA 7, HBD 0, PSA 76.8, QED 0.69
Compound (SMILES): Cc1nsc(-c2nnc3n2CCN(C(=O)c2ccc(Cl)cc2)[C@@H]3C)n1
InChIKey: ZMIOQWILBZBCHW-SECBINFHSA-N
Target: Neuromedin-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P29371
Assay: Competitive Binding Assay: The affinity of compounds of the invention for the human NK-3 receptor was determined by measuring the ability of compounds of the invention to competitively and reversibly displace a well-characterized NK-3 radioligand in a concentration-dependent manner.3H-SB222200 Binding Competition Assay with Human NK-3 ReceptorThe ability of compounds of the invention to inhibit the binding of the NK-3 receptor selective antagonist 3H-SB222200 was assessed by an in vitro radioligand binding assay. Membranes were prepared from Chinese hamster ovary recombinant cells stably expressing the human NK-3 receptor. The membranes were incubated with 5 nM 3H-SB222200 (ARC) in a HEPES 25 mM/NaCl 0.1M/CaCl2 1 mM/MgCl2 5 mM/BSA 0.5%/Saponin 10 μg/ml buffer at pH 7.4 and various concentrations of compounds of the invention. The amount of 3H-SB222200 bound to the receptor was determined after filtration by the quantification of membrane associated radioactivity using the TopCount-NXT reader (Packard).
Measurement: Ki = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 374.86, ALogP 2.98, HBA 7, HBD 0, PSA 76.8, QED 0.69
Compound (SMILES): C[C@@H]1c2nnc(-c3nc(C(F)(F)F)ns3)n2CCN1C(=O)c1ccc(F)cc1
InChIKey: RLKUYZTZCXMODG-MRVPVSSYSA-N
Target: Neuromedin-K receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P29371
Assay: Functional Assay: Chinese Hamster Ovary recombinant cells expressing the human NK-3 receptor and a construct that encodes the photoprotein apoaequorin were used for this assay. The antagonist activity of compounds of the invention is measured following pre-incubation (3 minutes) of the compound (at various concentrations) with the cells, followed by addition of the reference agonist (NKA) at a final concentration equivalent to the EC80 (3 nM) and recording of emitted light (FDSS 6000 Hamamatsu) over the subsequent 90-second period. The intensity of the emitted light is integrated using the reader software. Compound antagonist activity is measured based on the concentration-dependent inhibition of the luminescence response to the addition of Neurokinin A.
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 412.37, ALogP 3.17, HBA 7, HBD 0, PSA 76.8, QED 0.6
Compound (SMILES): Nc1ccccc1C(=O)Nc1cccc(F)c1
InChIKey: UUNGQEZMZQDIKE-UHFFFAOYSA-N
Target: Acyl-CoA (8-3)-desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O60427
Assay: Inhibition of liver delta-5 desaturase (unknown origin)
Measurement: IC50 = 516 nM (pChEMBL 6.289999961853027)
Descriptors: MW 230.24, ALogP 2.66, HBA 2, HBD 2, PSA 55.12, QED 0.78
Compound (SMILES): CC(C)c1cccc(NC(=O)c2ccccc2N)c1
InChIKey: MVETYYNURUWNBI-UHFFFAOYSA-N
Target: Acyl-CoA (8-3)-desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O60427
Assay: Inhibition of liver delta-5 desaturase (unknown origin)
Measurement: IC50 = 843 nM (pChEMBL 6.070000171661377)
Descriptors: MW 254.33, ALogP 3.64, HBA 2, HBD 2, PSA 55.12, QED 0.82
Compound (SMILES): Nc1ccc(F)cc1C(=O)Nc1cccc(Cl)c1
InChIKey: QUHFQPPVPNJRMZ-UHFFFAOYSA-N
Target: Acyl-CoA (8-3)-desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O60427
Assay: Inhibition of liver delta-5 desaturase (unknown origin)
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 264.69, ALogP 3.31, HBA 2, HBD 2, PSA 55.12, QED 0.82
Compound (SMILES): Nc1ccc(Cl)cc1C(=O)Nc1cccc(Cl)c1
InChIKey: QTPKSKMQWHTPTN-UHFFFAOYSA-N
Target: Acyl-CoA (8-3)-desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O60427
Assay: Inhibition of liver delta-5 desaturase (unknown origin)
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 281.14, ALogP 3.83, HBA 2, HBD 2, PSA 55.12, QED 0.82
Compound (SMILES): COc1ccc(O)c(C(=O)Nc2cccc(Cl)c2)c1
InChIKey: HZCXJTZFWWWHFF-UHFFFAOYSA-N
Target: Acyl-CoA (8-3)-desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O60427
Assay: Inhibition of liver delta-5 desaturase (unknown origin)
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 277.71, ALogP 3.31, HBA 3, HBD 2, PSA 58.56, QED 0.9
Compound (SMILES): CCOc1ccc(O)c(C(=O)Nc2cccc(Cl)c2)c1
InChIKey: ADBFRBWRIBULLJ-UHFFFAOYSA-N
Target: Acyl-CoA (8-3)-desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O60427
Assay: Inhibition of liver delta-5 desaturase (unknown origin)
Measurement: IC50 = 925 nM (pChEMBL 6.03000020980835)
Descriptors: MW 291.73, ALogP 3.7, HBA 3, HBD 2, PSA 58.56, QED 0.9
Compound (SMILES): Clc1cccc(Nc2ccnc3ccccc23)c1
InChIKey: OMEOWQXYEYRLGK-UHFFFAOYSA-N
Target: Acyl-CoA (8-3)-desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O60427
Assay: Inhibition of liver delta-5 desaturase (unknown origin)
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 254.72, ALogP 4.63, HBA 2, HBD 1, PSA 24.92, QED 0.72
Compound (SMILES): Clc1cccc(Nc2cccc3ccccc23)c1
InChIKey: QEYYTVWDRYNDJO-UHFFFAOYSA-N
Target: Acyl-CoA (8-3)-desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O60427
Assay: Inhibition of liver delta-5 desaturase (unknown origin)
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 253.73, ALogP 5.24, HBA 1, HBD 1, PSA 12.03, QED 0.66
Compound (SMILES): Clc1cccc(Nc2nccc3occc23)c1
InChIKey: QLYMHNFNFSMMHX-UHFFFAOYSA-N
Target: Acyl-CoA (8-3)-desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O60427
Assay: Inhibition of liver delta-5 desaturase (unknown origin)
Measurement: IC50 = 371 nM (pChEMBL 6.429999828338623)
Descriptors: MW 244.68, ALogP 4.22, HBA 3, HBD 1, PSA 38.06, QED 0.73
Compound (SMILES): Clc1cccc(Nc2ncnc3ccsc23)c1
InChIKey: YAPHXVGZFFXJBC-UHFFFAOYSA-N
Target: Acyl-CoA (8-3)-desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O60427
Assay: Inhibition of liver delta-5 desaturase (unknown origin)
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 261.74, ALogP 4.09, HBA 4, HBD 1, PSA 37.81, QED 0.76