lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cn1cc(-c2ccc3ncc4c(c3n2)n([C@H]2CC[C@H](O)CC2)c(=O)n4C)cn1
InChIKey: ZDEXVDRHVRCKFR-HDJSIYSDSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 7.18 nM (pChEMBL 8.140000343322754)
Descriptors: MW 378.44, ALogP 2.16, HBA 8, HBD 1, PSA 90.76, QED 0.58
Compound (SMILES): Cc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(C)CC2)c(=O)n4C)cn1
InChIKey: XRLJNYCQTCOLHF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 40.1 nM (pChEMBL 7.400000095367432)
Descriptors: MW 388.48, ALogP 2.92, HBA 7, HBD 0, PSA 68.84, QED 0.53
Compound (SMILES): Cc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(CC(N)=O)CC2)c(=O)n4C)cn1
InChIKey: YXFAAQVTSYIBFS-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 1.41 nM (pChEMBL 8.850000381469727)
Descriptors: MW 431.5, ALogP 1.78, HBA 8, HBD 1, PSA 111.93, QED 0.53
Compound (SMILES): Cc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(=O)CN(C)C)CC2)c(=O)n4C)cn1
InChIKey: JFMAOEQGINOHKN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 1.18 nM (pChEMBL 8.930000305175781)
Descriptors: MW 459.55, ALogP 2.38, HBA 8, HBD 0, PSA 89.15, QED 0.47
Compound (SMILES): Cc1ccc(-c2ccc3ncc4c(c3n2)n([C@H]2CC[C@H](O)CC2)c(=O)n4C)cn1
InChIKey: LVIORTDEPFZDSH-WKILWMFISA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 3.29 nM (pChEMBL 8.479999542236328)
Descriptors: MW 389.46, ALogP 3.13, HBA 7, HBD 1, PSA 85.83, QED 0.57
Compound (SMILES): Cc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(=O)CN)CC2)c(=O)n4C)cn1
InChIKey: WOXZNIHCGOBWSW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 3.84 nM (pChEMBL 8.420000076293945)
Descriptors: MW 431.5, ALogP 1.78, HBA 8, HBD 1, PSA 111.93, QED 0.53
Compound (SMILES): Cc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(=O)NN)CC2)c(=O)n4C)cn1
InChIKey: VNHKSWWLDVWBFT-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 1.06 nM (pChEMBL 8.970000267028809)
Descriptors: MW 432.49, ALogP 1.87, HBA 8, HBD 2, PSA 123.96, QED 0.28
Compound (SMILES): COc1ncc(-c2ccc3ncc4c(c3n2)n(C2CCN(C)CC2)c(=O)n4C)cn1
InChIKey: MZAXEMDPTLSROA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 4.51 nM (pChEMBL 8.350000381469727)
Descriptors: MW 405.46, ALogP 2.02, HBA 9, HBD 0, PSA 90.96, QED 0.51
Compound (SMILES): COc1ncc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(=O)CN(C)C)CC2)c(=O)n4C)cn1
InChIKey: UBJPZCYKCVGWGT-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 8.96 nM (pChEMBL 8.050000190734863)
Descriptors: MW 476.54, ALogP 1.47, HBA 10, HBD 0, PSA 111.27, QED 0.43
Compound (SMILES): COc1ncc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(=O)CN)CC2)c(=O)n4C)cn1
InChIKey: KKFNHCJVSBHRAF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 13.3 nM (pChEMBL 7.880000114440918)
Descriptors: MW 448.49, ALogP 0.87, HBA 10, HBD 1, PSA 134.05, QED 0.49
Compound (SMILES): COc1ncc(-c2ccc3ncc4c(c3n2)n(C2CCN(CCO)CC2)c(=O)n4C)cn1
InChIKey: SLCANOGAKHQGGN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 25.2 nM (pChEMBL 7.599999904632568)
Descriptors: MW 435.49, ALogP 1.38, HBA 10, HBD 1, PSA 111.19, QED 0.5
Compound (SMILES): COc1ncc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(C)=O)CC2)c(=O)n4C)cn1
InChIKey: FIEGXTNREZBMGI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 3.74 nM (pChEMBL 8.430000305175781)
Descriptors: MW 433.47, ALogP 1.93, HBA 9, HBD 0, PSA 108.03, QED 0.49
Compound (SMILES): COc1ncc(-c2ccc3ncc4c(c3n2)n(C2CCNCC2)c(=O)n4C)cn1
InChIKey: JECCEISTOFCAKU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 50.4 nM (pChEMBL 7.300000190734863)
Descriptors: MW 391.44, ALogP 1.67, HBA 9, HBD 1, PSA 99.75, QED 0.57
Compound (SMILES): CN(C)c1ccc(-c2ccc3ncc4c(c3n2)n(C2CCNCC2)c(=O)n4C)cn1
InChIKey: PWFKWGFNTXBANS-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 8.41 nM (pChEMBL 8.069999694824219)
Descriptors: MW 403.49, ALogP 2.34, HBA 8, HBD 1, PSA 80.87, QED 0.57
Compound (SMILES): N[C@H]1CC[C@H](n2c(=O)[nH]c3cnc4ccc(-c5cnc6ccccc6c5)nc4c32)CC1
InChIKey: GGPTUXLMOLCPJR-QAQDUYKDSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 3.33 nM (pChEMBL 8.479999542236328)
Descriptors: MW 410.48, ALogP 3.93, HBA 6, HBD 2, PSA 102.48, QED 0.46
Compound (SMILES): CC(=O)N1CCC(n2c(=O)n(C)c3cnc4ccc(-c5ccc(N(C)C)nc5)nc4c32)CC1
InChIKey: FDWYRWDMLCDEJO-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 1.72 nM (pChEMBL 8.760000228881836)
Descriptors: MW 445.53, ALogP 2.59, HBA 8, HBD 0, PSA 89.15, QED 0.48
Compound (SMILES): CNC(=O)N1CCC(n2c(=O)n(C)c3cnc4ccc(-c5ccc(N(C)C)nc5)nc4c32)CC1
InChIKey: GEFIJVBUAHDDEM-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against mTOR using an in vitro kinase assay. mTOR activity is measured in vitro by determining the level of phosphorylation of the protein substrate 4EBP-1. The phosphorylation of GFP-4E-BP1 at tyrosine residue is recognized by Ab Tb-anti-p4E-BP1, which results in time-resolved fluorescence resonance energy transfer (TR-FRET) between GFP and terbium in the Ab--product complex. Recombinant mTOR kinase domain, GFP-4E-BP1, and Lantha Ab Tb-anti-p4E-BP1, and TR-FRET dilution buffer were from Invitrogen. All other reagents were from Sigma. All assays were performed in a Corning white 384-well non-binding surface plate using Safire2 plate reader (TECAN) at room temperature. The assay buffer contained 50 mM HEPES pH 7.5, 0.01% polysorbate, 1 mM EGTA and 10 mM MnCl2. To the assay plate, substrate GFP-4E-BP-1 and mTOR in the assay buffer were mixed first and the reaction was initiated by addition of ATP.
Measurement: Ki = 3.01 nM (pChEMBL 8.520000457763672)
Descriptors: MW 460.54, ALogP 2.39, HBA 8, HBD 1, PSA 101.18, QED 0.5
Compound (SMILES): O=C(NCC(CC1CC1)c1cnc(C(F)(F)F)nc1)c1c(Cl)cccc1Cl
InChIKey: FUNGXBHNVRVIFC-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Binding Assay: Fluorescent Imaging Plate Reader (FLIPR) assay: Briefly, 293-human or mouse P2X7 stable cells were incubated in sucrose buffer, pH 7.4 [KCl (5 mM), NaH2PO4.2H2O (9.6 mM), HEPES (25 mM), sucrose (280 mM), glucose (5 mM), CaCl2 (0.5 mM), and probenecid (0.1425 g in 3 mL 1N NaOH was added for 500 mL solution)] in 384-well plates.293-rat P2X7 stable cells were incubated in HHPB (pH 7.4) [consisting of Hank's BSS (1×); HEPES (pH 7.4) (20 mM) (Sigma); probenecid (0.710g/5 mL 1N NaOH) (Sigma); and BSA (0.05%) (Roche) which was added after the pH had been adjusted] in 384-well plates. Fluo-4 NW dye mix (Molecular Probes, Inc., Eugene, Oreg., USA) was prepared in buffer (see manufacturer's instructions). Cell plates were removed from the 37° C. incubator, the media discarded and then 30 μL of dye was added to each well. Plates were placed in the 37° C., non-CO2 incubator for 30 minutes and then room temperature for 30 minutes.
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 418.25, ALogP 5.12, HBA 3, HBD 1, PSA 54.88, QED 0.71
Compound (SMILES): Cc1ncc(C(CNC(=O)c2cccc(Cl)c2Cl)C2CCC(F)(F)CC2)cn1
InChIKey: LFVFUUBRPMCKGZ-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: In Vitro Assay: Fluorescent Imaging Plate Reader (FLIPR) assay: Briefly, 293-human or mouse P2X7 stable cells were incubated in sucrose buffer, pH 7.4 [KCl (5 mM), NaH2PO4.2H2O (9.6 mM), HEPES (25 mM), sucrose (280 mM), glucose (5 mM), CaCl2 (0.5 mM), and probenecid (0.1425 g in 3 mL 1N NaOH was added for 500 mL solution)] in 384-well plates. 293-rat P2X7 stable cells were incubated in HHPB (pH 7.4) [consisting of Hank's BSS (1×); HEPES (pH 7.4) (20 mM) (Sigma); probenecid (0.710 g/5 mL 1N NaOH) (Sigma); and BSA (0.05%) (Roche) which was added after the pH had been adjusted] in 384-well plates. Fluo-4 NW dye mix (Molecular Probes, Inc., Eugene, Oreg., USA) was prepared in buffer (see manufacturer's instructions). Cell plates were removed from the 37° C. incubator, the media discarded and then 30 μL of dye was added to each well. Plates were placed in the 37° C., non-CO2 incubator for 30 minutes and then room temperature for 30 minutes.
Measurement: IC50 = 8.4 nM (pChEMBL 8.079999923706055)
Descriptors: MW 428.31, ALogP 5.43, HBA 3, HBD 1, PSA 54.88, QED 0.69
Compound (SMILES): NC1CCN(c2ccc(Nc3c(C(=O)C4CC4)cnc4ccc(-c5cc(Cl)c(O)c(Cl)c5)cc34)cn2)CC1
InChIKey: NDHPHGMWNYFSAA-UHFFFAOYSA-N
Target: Maternal embryonic leucine zipper kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q14680
Assay: Kinase Assay: MELK activity was determined in the presence or absence of compounds using fluorescein isothiocyanate-labeled (FITC-labeled) histone H3 peptide as a substrate. The extent of FITC-labeled histone H3 peptide phosphorylation was measured by immobilized metal ion affinity-based fluorescence polarization (IMAP) technology (Sportsman J R, et al., Assay Drug Dev. Technol. 2: 205-14, 2004) using IMAP FP Progressive Binding System (Molecular Devices Corporation). Test compounds were dissolved in DMSO at 12.5 mM and then serially diluted as the DMSO concentration in the assays to be 1%. The serially diluted compounds, 0.8 ng/micro-L PBK (Carna Biosciences) and 100 nM FITC-labeled histone H3 peptide were reacted in a reaction buffer (20 mM HEPES, 0.01% Tween-20, 0.3 mM MgCl2, 2 mM dithiothreitol, 50 micro-M ATP, pH 7.4) at room temperature for 1 hour. The reaction was stopped by the addition of three fold assay volume of progressive binding solution. Following 0.5 hour incubation at room temperature.
Measurement: IC50 = 5.6 nM (pChEMBL 8.25)
Descriptors: MW 548.47, ALogP 6.57, HBA 7, HBD 3, PSA 104.37, QED 0.23
Compound (SMILES): Cc1ccccc1CO[C@H]1CCCC1Nc1ncnc2c1ncn2C1O[C@H](CO)[C@@H](O)[C@H]1O
InChIKey: FWRDMMCMCWVHLP-UNYIAIFGSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Binding Assay: The compounds were studied in binding assays to determine selectivity and potency to A1, A2a and A3 adenosine receptors.
Measurement: Ki = 5320 nM (pChEMBL 5.269999980926514)
Descriptors: MW 455.52, ALogP 1.3, HBA 10, HBD 4, PSA 134.78, QED 0.42
Compound (SMILES): OC[C@H]1OC(n2cnc3c(NC4CCC[C@@H]4OCc4cccc(F)c4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: CYHRDMKKFSGMNK-XCUHZOMWSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Oryctolagus cuniculus
UniProt: O02667
Assay: Binding Assay: The compounds were studied in binding assays to determine selectivity and potency to A1, A2a and A3 adenosine receptors.
Measurement: Ki = 1570 nM (pChEMBL 5.800000190734863)
Descriptors: MW 459.48, ALogP 1.13, HBA 10, HBD 4, PSA 134.78, QED 0.41
Compound (SMILES): OC[C@H]1OC(n2cnc3c(NC4CCC[C@@H]4OCc4ccc(F)cc4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: PRXZAKNIYXOOMQ-XCUHZOMWSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Oryctolagus cuniculus
UniProt: O02667
Assay: Binding Assay: The compounds were studied in binding assays to determine selectivity and potency to A1, A2a and A3 adenosine receptors.
Measurement: Ki = 1630 nM (pChEMBL 5.789999961853027)
Descriptors: MW 459.48, ALogP 1.13, HBA 10, HBD 4, PSA 134.78, QED 0.41
Compound (SMILES): CC(C)c1ccc(CO[C@H]2CCCC2Nc2ncnc3c2ncn3C2O[C@H](CO)[C@@H](O)[C@H]2O)cc1
InChIKey: HEHPEMPIIGZAPY-FNAJLOLUSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Oryctolagus cuniculus
UniProt: O02667
Assay: Binding Assay: The compounds were studied in binding assays to determine selectivity and potency to A1, A2a and A3 adenosine receptors.
Measurement: Ki = 1870 nM (pChEMBL 5.730000019073486)
Descriptors: MW 483.57, ALogP 2.11, HBA 10, HBD 4, PSA 134.78, QED 0.38
Compound (SMILES): OC[C@H]1OC(n2cnc3c(NC4CCC[C@@H]4OCc4cccc(I)c4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: HZBFCOYWEGAJGZ-XCUHZOMWSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Oryctolagus cuniculus
UniProt: O02667
Assay: Binding Assay: The compounds were studied in binding assays to determine selectivity and potency to A1, A2a and A3 adenosine receptors.
Measurement: Ki = 1290 nM (pChEMBL 5.889999866485596)
Descriptors: MW 567.38, ALogP 1.59, HBA 10, HBD 4, PSA 134.78, QED 0.31
Compound (SMILES): COc1cccc(CO[C@H]2CCCC2Nc2ncnc3c2ncn3C2O[C@H](CO)[C@@H](O)[C@H]2O)c1
InChIKey: DKXQAUQBUSRNHS-UNYIAIFGSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Oryctolagus cuniculus
UniProt: O02667
Assay: Binding Assay: The compounds were studied in binding assays to determine selectivity and potency to A1, A2a and A3 adenosine receptors.
Measurement: Ki = 1290 nM (pChEMBL 5.889999866485596)
Descriptors: MW 471.51, ALogP 1, HBA 11, HBD 4, PSA 144.01, QED 0.38
Compound (SMILES): Cc1cccc(CO[C@H]2CCCC2Nc2nc(Cl)nc3c2ncn3C2O[C@H](CO)[C@@H](O)[C@H]2O)c1
InChIKey: NYDFVRTWEYFDIK-XCUHZOMWSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Oryctolagus cuniculus
UniProt: P34970
Assay: Binding Assay: The compounds were studied in binding assays to determine selectivity and potency to A1, A2a and A3 adenosine receptors.
Measurement: Ki = 12.3 nM (pChEMBL 7.909999847412109)
Descriptors: MW 489.96, ALogP 1.95, HBA 10, HBD 4, PSA 134.78, QED 0.37
Compound (SMILES): Cc1ccccc1CO[C@@H]1CCCC1Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
InChIKey: FWRDMMCMCWVHLP-FJPLYAHASA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Oryctolagus cuniculus
UniProt: P34970
Assay: Binding Assay: The compounds were studied in binding assays to determine selectivity and potency to A1, A2a and A3 adenosine receptors.
Measurement: Ki = 2.65 nM (pChEMBL 8.579999923706055)
Descriptors: MW 455.52, ALogP 1.3, HBA 10, HBD 4, PSA 134.78, QED 0.42
Compound (SMILES): OC[C@H]1O[C@@H](n2cnc3c(NC4CCC[C@H]4OCc4cccc(F)c4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: CYHRDMKKFSGMNK-HFALVTKESA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Oryctolagus cuniculus
UniProt: O02667
Assay: Binding Assay: The compounds were studied in binding assays to determine selectivity and potency to A1, A2a and A3 adenosine receptors.
Measurement: Ki = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 459.48, ALogP 1.13, HBA 10, HBD 4, PSA 134.78, QED 0.41
Compound (SMILES): OC[C@H]1O[C@@H](n2cnc3c(NC4CCC[C@H]4OCc4ccc(F)cc4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: PRXZAKNIYXOOMQ-HFALVTKESA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Oryctolagus cuniculus
UniProt: O02667
Assay: Binding Assay: The compounds were studied in binding assays to determine selectivity and potency to A1, A2a and A3 adenosine receptors.
Measurement: Ki = 4040 nM (pChEMBL 5.389999866485596)
Descriptors: MW 459.48, ALogP 1.13, HBA 10, HBD 4, PSA 134.78, QED 0.41
Compound (SMILES): CC(C)c1ccc(CO[C@@H]2CCCC2Nc2ncnc3c2ncn3[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)cc1
InChIKey: HEHPEMPIIGZAPY-JSNTWKLXSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Binding Assay: The compounds were studied in binding assays to determine selectivity and potency to A1, A2a and A3 adenosine receptors.
Measurement: Ki = 3780 nM (pChEMBL 5.420000076293945)
Descriptors: MW 483.57, ALogP 2.11, HBA 10, HBD 4, PSA 134.78, QED 0.38
Compound (SMILES): OC[C@H]1O[C@@H](n2cnc3c(NC4CCC[C@H]4OCc4cccc(I)c4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: HZBFCOYWEGAJGZ-HFALVTKESA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Oryctolagus cuniculus
UniProt: O02667
Assay: Binding Assay: The compounds were studied in binding assays to determine selectivity and potency to A1, A2a and A3 adenosine receptors.
Measurement: Ki = 3380 nM (pChEMBL 5.46999979019165)
Descriptors: MW 567.38, ALogP 1.59, HBA 10, HBD 4, PSA 134.78, QED 0.31
Compound (SMILES): COc1cccc(CO[C@@H]2CCCC2Nc2ncnc3c2ncn3[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c1
InChIKey: DKXQAUQBUSRNHS-FJPLYAHASA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Oryctolagus cuniculus
UniProt: P34970
Assay: Binding Assay: The compounds were studied in binding assays to determine selectivity and potency to A1, A2a and A3 adenosine receptors.
Measurement: Ki = 5.59 nM (pChEMBL 8.25)
Descriptors: MW 471.51, ALogP 1, HBA 11, HBD 4, PSA 144.01, QED 0.38
Compound (SMILES): Cc1cccc(C)c1CO[C@@H]1CCCC1Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
InChIKey: ORFNSVWTHZCZKK-LDSVTMFDSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Binding Assay: The compounds were studied in binding assays to determine selectivity and potency to A1, A2a and A3 adenosine receptors.
Measurement: Ki = 2270 nM (pChEMBL 5.639999866485596)
Descriptors: MW 469.54, ALogP 1.6, HBA 10, HBD 4, PSA 134.78, QED 0.41
Compound (SMILES): COC(=O)C1(NC(=O)C2=C(O)[C@@H]3Oc4c(O)ccc5c4[C@@]34CCN(CC3CC3)[C@H](C5)[C@]4(O)C2)CC1
InChIKey: XVCJWAXHXOUVTJ-GZIHESCCSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DAMGO from recombinant human mu-opioid receptor expressed in CHOK1 cells
Measurement: Ki = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 482.53, ALogP 1.2, HBA 8, HBD 4, PSA 128.56, QED 0.46
Compound (SMILES): CC(C)(C)c1[nH]nc2c1C(c1ccccc1OCC(=O)O)N(c1ccc(-c3ccon3)cc1)C2=O
InChIKey: RPPBNXPYURTLBF-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 472.5, ALogP 4.58, HBA 6, HBD 2, PSA 121.55, QED 0.42
Compound (SMILES): CCOC(=O)c1ccc(N2C(=O)c3n[nH]c(C(C)(C)C)c3C2c2ccccc2OC)cc1
InChIKey: ZQIRBVQPHGRYRK-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 433.51, ALogP 4.64, HBA 5, HBD 1, PSA 84.52, QED 0.59
Compound (SMILES): CC(C)(C)c1[nH]nc2c1C(c1ccccc1OCCO)N(c1ccc(-c3ccon3)cc1)C2=O
InChIKey: KULIBONXHNHSRK-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 458.52, ALogP 4.48, HBA 6, HBD 2, PSA 104.48, QED 0.44
Compound (SMILES): O=C(Cc1cccc(OC(F)(F)F)c1)Nc1ccc(CCCCc2nnc(NC(=O)Cc3ccccn3)s2)nn1
InChIKey: PRAAPINBUWJLGA-UHFFFAOYSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Binding affinity to human GLS1 expressed in Escherichia coli strain BL21 (DE3)pLysS by SPR assay
Measurement: Kd = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 571.59, ALogP 4.55, HBA 9, HBD 2, PSA 131.88, QED 0.24
Compound (SMILES): CCOC(=O)Nc1nnc(CCCCc2nnc(NC(=O)Cc3ccccc3)s2)s1
InChIKey: KDTCCUCQJBWMAC-UHFFFAOYSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Enzyme Assay: Compounds were assessed for their ability to inhibit the enzymatic activity of a recombinant form of Glutaminase 1 (GAC) using a biochemical assay that couples the production of glutamate (liberated by GAC) to glutamate dehydrogenase (GDH) and measuring the change in absorbance for the reduction of NAD+ to NADH.
Measurement: IC50 = 810 nM (pChEMBL 6.090000152587891)
Descriptors: MW 446.56, ALogP 3.7, HBA 9, HBD 2, PSA 118.99, QED 0.46
Compound (SMILES): NC1=N[C@@H](c2ccccc2Cl)CO1
InChIKey: QMVBXTOPWLYMTJ-MRVPVSSYSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Agonist activity at rat TAAR1 expressed in recombinant HEK293 cells assessed as cAMP accumulation after 30 mins by luminometer
Measurement: EC50 = 87 nM (pChEMBL 7.059999942779541)
Descriptors: MW 196.64, ALogP 1.73, HBA 3, HBD 1, PSA 47.61, QED 0.74
Compound (SMILES): NC1=N[C@@H](c2ccc(Cl)c(Cl)c2)CO1
InChIKey: HGGPGNSCBBAGJN-MRVPVSSYSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Agonist activity at rat TAAR1 expressed in recombinant HEK293 cells assessed as cAMP accumulation after 30 mins by luminometer
Measurement: EC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 231.08, ALogP 2.38, HBA 3, HBD 1, PSA 47.61, QED 0.81
Compound (SMILES): NC1=N[C@@H](c2ccc(Br)cc2)CO1
InChIKey: CWSFSFQMKPGYPP-MRVPVSSYSA-N
Target: Trace amine-associated receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q923Y9
Assay: Agonist activity at rat TAAR1 expressed in recombinant HEK293 cells assessed as cAMP accumulation after 30 mins by luminometer
Measurement: EC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 241.09, ALogP 1.84, HBA 3, HBD 1, PSA 47.61, QED 0.81
Compound (SMILES): O=C(/C=C/CN1CCCCC1)Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCC(F)F
InChIKey: ICDUDMAKDBBZOT-SNAWJCMRSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: ELISA-Based Kinase Assay: Inhibition of erbB tyrosine kinase activity was assessed using an ELISA-based receptor tyrosine kinase assay. Kinase reactions (50 mM HEPES, pH 7.4, 125 mM NaCl, 10 mM MgCl2, 100 μM sodium orthovanadate, 2 mM dithiothreitol, 20 uM ATP, test compound or vehicle control and 1-5 nM GST-erbB per 50 uL reaction) were run in 96-well plates coated with 0.25 mg/ml poly-Glu-Tyr (Sigma). The reactions were incubated for 6 minutes at room temperature while shaking. Kinase reactions were stopped by removal of reaction mixture, then wells were washed with wash buffer comprising 3% Bovine Serum Albumin and 0.1% Tween 20 in Phosphate Buffered Saline (PBS). Phosphorylated tyrosine residues were detected by adding 0.2 μg/ml anti-phosphotyrosine antibody (Oncogene Ab-4; 50 μL/well) coupled to Horse Radish Peroxidase (HRP) for 25 minutes while shaking at room temperature.
Measurement: IC50 = 244.39 nM (pChEMBL 6.610000133514404)
Descriptors: MW 519.96, ALogP 5.79, HBA 6, HBD 2, PSA 79.38, QED 0.35
Compound (SMILES): O=C(/C=C/CN1CCCCC1)Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1OCCCN1CCOCC1
InChIKey: CJIJVEOGUOJOMJ-GQCTYLIASA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: ELISA-Based Kinase Assay: Inhibition of erbB tyrosine kinase activity was assessed using an ELISA-based receptor tyrosine kinase assay. Kinase reactions (50 mM HEPES, pH 7.4, 125 mM NaCl, 10 mM MgCl2, 100 μM sodium orthovanadate, 2 mM dithiothreitol, 20 uM ATP, test compound or vehicle control and 1-5 nM GST-erbB per 50 uL reaction) were run in 96-well plates coated with 0.25 mg/ml poly-Glu-Tyr (Sigma). The reactions were incubated for 6 minutes at room temperature while shaking. Kinase reactions were stopped by removal of reaction mixture, then wells were washed with wash buffer comprising 3% Bovine Serum Albumin and 0.1% Tween 20 in Phosphate Buffered Saline (PBS). Phosphorylated tyrosine residues were detected by adding 0.2 μg/ml anti-phosphotyrosine antibody (Oncogene Ab-4; 50 μL/well) coupled to Horse Radish Peroxidase (HRP) for 25 minutes while shaking at room temperature.
Measurement: IC50 = 84.05 nM (pChEMBL 7.079999923706055)
Descriptors: MW 583.11, ALogP 5.25, HBA 8, HBD 2, PSA 91.85, QED 0.23
Compound (SMILES): COc1cc2ncnc(Nc3ccc(F)c(Cl)c3)c2cc1NC(=O)/C=C/CN1CCCC(F)C1
InChIKey: XFXOYVZSTQCSQN-HWKANZROSA-N
Target: Receptor tyrosine-protein kinase erbB-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15303
Assay: ELISA-Based Kinase Assay: Inhibition of erbB tyrosine kinase activity was assessed using an ELISA-based receptor tyrosine kinase assay. Kinase reactions (50 mM HEPES, pH 7.4, 125 mM NaCl, 10 mM MgCl2, 100 μM sodium orthovanadate, 2 mM dithiothreitol, 20 uM ATP, test compound or vehicle control and 1-5 nM GST-erbB per 50 uL reaction) were run in 96-well plates coated with 0.25 mg/ml poly-Glu-Tyr (Sigma). The reactions were incubated for 6 minutes at room temperature while shaking. Kinase reactions were stopped by removal of reaction mixture, then wells were washed with wash buffer comprising 3% Bovine Serum Albumin and 0.1% Tween 20 in Phosphate Buffered Saline (PBS). Phosphorylated tyrosine residues were detected by adding 0.2 μg/ml anti-phosphotyrosine antibody (Oncogene Ab-4; 50 μL/well) coupled to Horse Radish Peroxidase (HRP) for 25 minutes while shaking at room temperature.
Measurement: IC50 = 233.8 nM (pChEMBL 6.630000114440918)
Descriptors: MW 487.94, ALogP 5.1, HBA 6, HBD 2, PSA 79.38, QED 0.45
Compound (SMILES): COc1cc2ncnc(Nc3ccc(F)c(Cl)c3)c2cc1NC(=O)/C=C/CN1CCC(F)CC1
InChIKey: YMQSEEOAYCTNQU-NSCUHMNNSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: ELISA-Based Kinase Assay: Inhibition of erbB tyrosine kinase activity was assessed using an ELISA-based receptor tyrosine kinase assay. Kinase reactions (50 mM HEPES, pH 7.4, 125 mM NaCl, 10 mM MgCl2, 100 μM sodium orthovanadate, 2 mM dithiothreitol, 20 uM ATP, test compound or vehicle control and 1-5 nM GST-erbB per 50 uL reaction) were run in 96-well plates coated with 0.25 mg/ml poly-Glu-Tyr (Sigma). The reactions were incubated for 6 minutes at room temperature while shaking. Kinase reactions were stopped by removal of reaction mixture, then wells were washed with wash buffer comprising 3% Bovine Serum Albumin and 0.1% Tween 20 in Phosphate Buffered Saline (PBS). Phosphorylated tyrosine residues were detected by adding 0.2 μg/ml anti-phosphotyrosine antibody (Oncogene Ab-4; 50 μL/well) coupled to Horse Radish Peroxidase (HRP) for 25 minutes while shaking at room temperature.
Measurement: IC50 = 247.12 nM (pChEMBL 6.610000133514404)
Descriptors: MW 487.94, ALogP 5.1, HBA 6, HBD 2, PSA 79.38, QED 0.45
Compound (SMILES): COc1cc2ncnc(Nc3ccc(F)c(Cl)c3)c2cc1NC(=O)/C=C/CN1CCCCCC1
InChIKey: HNVQCOJZTIBBPB-VOTSOKGWSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: ELISA-Based Kinase Assay: Inhibition of erbB tyrosine kinase activity was assessed using an ELISA-based receptor tyrosine kinase assay. Kinase reactions (50 mM HEPES, pH 7.4, 125 mM NaCl, 10 mM MgCl2, 100 μM sodium orthovanadate, 2 mM dithiothreitol, 20 uM ATP, test compound or vehicle control and 1-5 nM GST-erbB per 50 uL reaction) were run in 96-well plates coated with 0.25 mg/ml poly-Glu-Tyr (Sigma). The reactions were incubated for 6 minutes at room temperature while shaking. Kinase reactions were stopped by removal of reaction mixture, then wells were washed with wash buffer comprising 3% Bovine Serum Albumin and 0.1% Tween 20 in Phosphate Buffered Saline (PBS). Phosphorylated tyrosine residues were detected by adding 0.2 μg/ml anti-phosphotyrosine antibody (Oncogene Ab-4; 50 μL/well) coupled to Horse Radish Peroxidase (HRP) for 25 minutes while shaking at room temperature.
Measurement: IC50 = 12.13 nM (pChEMBL 7.920000076293945)
Descriptors: MW 483.98, ALogP 5.55, HBA 6, HBD 2, PSA 79.38, QED 0.43
Compound (SMILES): CC(=O)N1CCc2nc(Nc3ncc4c5ccncc5n([C@H]5CC[C@H](C)CC5)c4n3)ccc2C1
InChIKey: YJRPVMCKBPJNKR-RUCARUNLSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: Kinase Assay: The CDK4 and CDK1 inhibitory activity of the CDK4/6-FLT3 inhibitors was determined with a filtration kinase assay. The compounds, kinase and substrate diluted in the kinase buffer (20 mM Tris, pH7.4, 50 mM NaCl, 1 mM DTT, 0.1% BSA) were sequentially added to a 96-well Multiscreen HTS filtration plate (Millipore). The final 100 μL reaction mixture in each well contained 0.3 μg of CDK4/Cyclin D1 or CDK1/Cyclin B (Cell Signaling Technology), 1 μg of Rb fragment (aa773-928, Millipore) for the CDK4 assay or 5 μg of histone H1 for the CDK1 assay and 1 μCi of [33P]-ATP. The mixture was incubated at room temperature for 1 hour. The proteins in the reaction were then precipitated and washed with cold TCA solution using an aspiration/filtration vacuum system. The plates were dried at room temperature, and the retained radioactivity was measured by scintillation counting.
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 455.57, ALogP 4.77, HBA 7, HBD 1, PSA 88.83, QED 0.48
Compound (SMILES): CN(CCO)c1ccc(C(=O)Nc2cccc(CNc3ncnc4c(C(N)=O)cccc34)c2)cn1
InChIKey: QCETXMLIFLYKQH-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase beta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23443
Assay: Enzyme Assay: P70S6K inhibitor compounds are diluted and plated in 96 well plates. A reaction mixture including the following components is then added to the compound plate to initiate the enzyme reaction; P70S6K (3 nM, T412E mutant, Millipore) is mixed with 24 μM ATP in an assay buffer containing 100 mM Hepes (pH 7.5), 5 mM MgCl2, 1 mM DTT, 0.015% Brij and 1 μM of the substrate peptide FITC-AHA-AKRRRLSSLRA-OH (derived from the S6 ribosomal protein sequence, FITC=fluorescein isothiocyanate, AHA=6-aminohexanoic acid). The reaction is incubated for 90 min at 25° C., before the addition of 10 mM EDTA to stop the reaction. The proportion of substrate and product (phosphorylated) peptide is analysed on a Caliper Life Sciences Lab Chip 3000, using a pressure of −1.4 psi, and upstream and downstream voltages of −3000 and −700 respectively.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 471.52, ALogP 2.42, HBA 8, HBD 4, PSA 146.36, QED 0.29
Compound (SMILES): CC(Nc1ncnc2c(C(N)=O)cccc12)c1cccc(NC(=O)c2ccccc2)c1
InChIKey: UUVFRMLWZBOAOM-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase beta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23443
Assay: Enzyme Assay: P70S6K inhibitor compounds are diluted and plated in 96 well plates. A reaction mixture including the following components is then added to the compound plate to initiate the enzyme reaction; P70S6K (3 nM, T412E mutant, Millipore) is mixed with 24 μM ATP in an assay buffer containing 100 mM Hepes (pH 7.5), 5 mM MgCl2, 1 mM DTT, 0.015% Brij and 1 μM of the substrate peptide FITC-AHA-AKRRRLSSLRA-OH (derived from the S6 ribosomal protein sequence, FITC=fluorescein isothiocyanate, AHA=6-aminohexanoic acid). The reaction is incubated for 90 min at 25° C., before the addition of 10 mM EDTA to stop the reaction. The proportion of substrate and product (phosphorylated) peptide is analysed on a Caliper Life Sciences Lab Chip 3000, using a pressure of −1.4 psi, and upstream and downstream voltages of −3000 and −700 respectively.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 411.47, ALogP 4.15, HBA 5, HBD 3, PSA 110, QED 0.44
Compound (SMILES): NC(=O)C1=c2ncnc(NC(CCN3CCCC3)c3cccc(NC(=O)c4ccc(Br)cc4)c3)c2=CCC1
InChIKey: PDULEZONFAQVLI-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase beta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23443
Assay: Enzyme Assay: P70S6K inhibitor compounds are diluted and plated in 96 well plates. A reaction mixture including the following components is then added to the compound plate to initiate the enzyme reaction; P70S6K (3 nM, T412E mutant, Millipore) is mixed with 24 μM ATP in an assay buffer containing 100 mM Hepes (pH 7.5), 5 mM MgCl2, 1 mM DTT, 0.015% Brij and 1 μM of the substrate peptide FITC-AHA-AKRRRLSSLRA-OH (derived from the S6 ribosomal protein sequence, FITC=fluorescein isothiocyanate, AHA=6-aminohexanoic acid). The reaction is incubated for 90 min at 25° C., before the addition of 10 mM EDTA to stop the reaction. The proportion of substrate and product (phosphorylated) peptide is analysed on a Caliper Life Sciences Lab Chip 3000, using a pressure of −1.4 psi, and upstream and downstream voltages of −3000 and −700 respectively.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 575.51, ALogP 3.34, HBA 6, HBD 3, PSA 113.24, QED 0.36