lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cn1c(=O)n(C2CCN(C(=O)CO)CC2)c2c3nc(-c4ccnc5[nH]ncc45)ccc3ncc21
InChIKey: BQFCMZRCBOMMDE-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 = 1.77 nM (pChEMBL 8.75)
Descriptors: MW 458.48, ALogP 1.38, HBA 9, HBD 2, PSA 134.82, QED 0.42
Compound (SMILES): C[C@H](O)C(=O)N1CCC(n2c(=O)n(C)c3cnc4ccc(-c5ccnc6[nH]ncc56)nc4c32)CC1
InChIKey: WJLXKJVDEMAVDD-ZDUSSCGKSA-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 = 1.69 nM (pChEMBL 8.770000457763672)
Descriptors: MW 472.51, ALogP 1.77, HBA 9, HBD 2, PSA 134.82, QED 0.41
Compound (SMILES): Cn1c(=O)n(C2CCN(C(=O)CO)CC2)c2c3nc(-c4cccc5[nH]ncc45)ccc3ncc21
InChIKey: OYXDADGCFDOKLT-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 = 1.97 nM (pChEMBL 8.710000038146973)
Descriptors: MW 457.49, ALogP 1.98, HBA 8, HBD 2, PSA 121.93, QED 0.43
Compound (SMILES): C[C@@H](O)C(=O)N1CCC(n2c(=O)n(C)c3cnc4ccc(-c5cnc6[nH]ncc6c5)nc4c32)CC1
InChIKey: ZQVPQBARVVEJLR-CYBMUJFWSA-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 = 0.241 nM (pChEMBL 9.619999885559082)
Descriptors: MW 472.51, ALogP 1.77, HBA 9, HBD 2, PSA 134.82, QED 0.41
Compound (SMILES): COCC(=O)N1CCC(n2c(=O)n(C)c3cnc4ccc(-c5cnc6[nH]ncc6c5)nc4c32)CC1
InChIKey: RRBZGDINLXZGOF-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 = 0.323 nM (pChEMBL 9.489999771118164)
Descriptors: MW 472.51, ALogP 2.03, HBA 9, HBD 1, PSA 123.82, QED 0.42
Compound (SMILES): Cn1c(=O)n(C2CCN(C(=O)C(C)(C)O)CC2)c2c3nc(-c4cnc5[nH]ncc5c4)ccc3ncc21
InChIKey: CRGQBIGNXMYDSX-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 = 0.658 nM (pChEMBL 9.180000305175781)
Descriptors: MW 486.54, ALogP 2.16, HBA 9, HBD 2, PSA 134.82, QED 0.4
Compound (SMILES): Cn1c(=O)n(C2CCN(C(=O)CO)CC2)c2c3nc(-c4cnc5[nH]ncc5c4)ccc3ncc21
InChIKey: HNHGXYRBEMGQQH-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 = 4.06 nM (pChEMBL 8.390000343322754)
Descriptors: MW 458.48, ALogP 1.38, HBA 9, HBD 2, PSA 134.82, QED 0.42
Compound (SMILES): CN1CCC(n2c(=O)n(C)c3cnc4ccc(-c5cnc6[nH]ncc6c5)nc4c32)CC1
InChIKey: BCLLEOJYENBBDN-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 = 5.67 nM (pChEMBL 8.25)
Descriptors: MW 414.47, ALogP 2.49, HBA 8, HBD 1, PSA 97.52, QED 0.48
Compound (SMILES): CCNC(=O)Nc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(=O)OC(C)(C)C)CC2)c(=O)n4C)cc1
InChIKey: SSCOZTIRCZPKOI-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 = 14.4 nM (pChEMBL 7.840000152587891)
Descriptors: MW 545.64, ALogP 4.66, HBA 8, HBD 2, PSA 123.38, QED 0.38
Compound (SMILES): COc1ccc(-c2ccc3ncc4c(c3n2)n(CCN2CCNCC2)c(=O)n4C)cn1
InChIKey: KLHGJLLNTSJYSP-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 = 273 nM (pChEMBL 6.559999942779541)
Descriptors: MW 419.49, ALogP 1.26, HBA 9, HBD 1, PSA 90.1, QED 0.52
Compound (SMILES): Cn1c(=O)n([C@H]2CC[C@H](O)CC2)c2c3nc(-c4ccc5[nH]ncc5c4)ccc3ncc21
InChIKey: ZLASBNFOQVWTOW-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 = 0.359 nM (pChEMBL 9.449999809265137)
Descriptors: MW 414.47, ALogP 3.3, HBA 7, HBD 2, PSA 101.62, QED 0.46
Compound (SMILES): Cn1c(=O)n([C@H]2CC[C@H](O)CC2)c2c3nc(-c4cnc5[nH]ncc5c4)ccc3ncc21
InChIKey: SRIMYUDGKMDALL-SHTZXODSSA-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 = 0.117 nM (pChEMBL 9.930000305175781)
Descriptors: MW 415.46, ALogP 2.7, HBA 8, HBD 2, PSA 114.51, QED 0.46
Compound (SMILES): COc1ccc(-c2ccc3ncc4c(c3n2)n(CCN2CCOCC2)c(=O)n4C)cn1
InChIKey: IVCZYXCKEYXMLR-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 = 27.8 nM (pChEMBL 7.559999942779541)
Descriptors: MW 420.47, ALogP 1.69, HBA 9, HBD 0, PSA 87.3, QED 0.49
Compound (SMILES): COCCn1c(=O)n(C)c2cnc3ccc(-c4ccc(OC)nc4)nc3c21
InChIKey: MLKZQLZLWPQANJ-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 = 7.13 nM (pChEMBL 8.149999618530273)
Descriptors: MW 365.39, ALogP 2, HBA 8, HBD 0, PSA 84.06, QED 0.54
Compound (SMILES): COc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(=O)[C@H](C)O)CC2)c(=O)n4C)cc1
InChIKey: QRJAMQLBQFQSCP-HNNXBMFYSA-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 = 1.94 nM (pChEMBL 8.710000038146973)
Descriptors: MW 461.52, ALogP 2.5, HBA 8, HBD 1, PSA 102.48, QED 0.5
Compound (SMILES): COc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(=O)CO)CC2)c(=O)n4C)cc1
InChIKey: AVPPVPMWQXGOOV-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 = 3.42 nM (pChEMBL 8.470000267028809)
Descriptors: MW 447.5, ALogP 2.11, HBA 8, HBD 1, PSA 102.48, QED 0.51
Compound (SMILES): COc1ccc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(C)=O)CC2)c(=O)n4C)cc1
InChIKey: AMXYSLJPYNAHGL-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 = 14.6 nM (pChEMBL 7.840000152587891)
Descriptors: MW 431.5, ALogP 3.14, HBA 7, HBD 0, PSA 82.25, QED 0.5
Compound (SMILES): COc1cccc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(=O)[C@H](C)O)CC2)c(=O)n4C)c1
InChIKey: HLENCPWDVNHNST-HNNXBMFYSA-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 = 8.51 nM (pChEMBL 8.069999694824219)
Descriptors: MW 461.52, ALogP 2.5, HBA 8, HBD 1, PSA 102.48, QED 0.5
Compound (SMILES): COc1cccc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(=O)CO)CC2)c(=O)n4C)c1
InChIKey: LNYJFNGCMKEZBH-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 = 10.2 nM (pChEMBL 7.989999771118164)
Descriptors: MW 447.5, ALogP 2.11, HBA 8, HBD 1, PSA 102.48, QED 0.51
Compound (SMILES): COc1cccc(-c2ccc3ncc4c(c3n2)n(C2CCN(C(C)=O)CC2)c(=O)n4C)c1
InChIKey: VSQITRQCJYCJJW-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 = 10.3 nM (pChEMBL 7.989999771118164)
Descriptors: MW 431.5, ALogP 3.14, HBA 7, HBD 0, PSA 82.25, QED 0.5
Compound (SMILES): COc1ccccc1-c1ccc2ncc3c(c2n1)n(C1CCN(C(=O)CO)CC1)c(=O)n3C
InChIKey: GRHZRVMBLWRWPF-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Biochemical Assay: Compounds of the present invention were evaluated for potency against PI3-Kalpha using an in vitro kinase assay. PI3-Kalpha activity is measured in vitro by determining the level of phosphorylation of the substrate PI(4,5)P2. The formation of product PI(3,4,5)P3 is monitored by binding to the Grip1 PH domain in a ligand displacement fluorescence polarization (FP) assay, in which the TAMRA-labeled PI(3,4,5)P3 complexed with Grip1 PH domain is displaced by PI(3,4,5)P3 formed in the PI3-Kalpha reaction resulting in a decrease in FP signal. Mouse PI3-Kalpha P110 and P85 subunits were co-expressed in insect cells and co-purified to homogeneity. PI(4,5)P2 were obtained from Cayman. TAMRA-labeled PI(3,4,5)P3 were from Echelon, Grip1 PH domain from Dundee and other reagents were from Sigma. All assays were performed in a Corning solid black 96-well half area plate using LJL Analyst (Molecular Devices) at room temperature. The assay buffer contained 50 mM HEPES, pH 7.4, 150 mM NaCl.
Measurement: Ki = 292 nM (pChEMBL 6.539999961853027)
Descriptors: MW 447.5, ALogP 2.11, HBA 8, HBD 1, PSA 102.48, QED 0.51
Compound (SMILES): Nc1ncnn2c(-c3ccnc(F)c3)cc(C(=O)N[C@H]3CC[C@H](O)CC3)c12
InChIKey: DZUXIHIXWCKJDW-HAQNSBGRSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates. Incorporation of radioactive phosphate into the peptide substrate was determined.
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 370.39, ALogP 1.55, HBA 7, HBD 3, PSA 118.43, QED 0.6
Compound (SMILES): CCOC(=O)NC1CCC(NC(=O)c2cc(-c3ccnc(OC)c3)n3ncnc(N)c23)CC1
InChIKey: UOUCFNDSPAGXJQ-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates. Incorporation of radioactive phosphate into the peptide substrate was determined.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 453.5, ALogP 2.17, HBA 9, HBD 3, PSA 145.76, QED 0.51
Compound (SMILES): CCOC(=O)N[C@H]1CC[C@H](NC(=O)c2cc(-c3ccncc3)n3ncnc(N)c23)CC1
InChIKey: JJHBNGJYDQCBGI-SHTZXODSSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates. Incorporation of radioactive phosphate into the peptide substrate was determined.
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 423.48, ALogP 2.16, HBA 8, HBD 3, PSA 136.53, QED 0.57
Compound (SMILES): CNCCCNC(=O)c1cc(-c2ccncc2)n2ncnc(N)c12
InChIKey: XOPYMNICVOZWGG-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates. Incorporation of radioactive phosphate into the peptide substrate was determined.
Measurement: IC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 325.38, ALogP 0.71, HBA 7, HBD 3, PSA 110.23, QED 0.58
Compound (SMILES): CC(=O)NC1CCC(NC(=O)c2cc(-c3ccncc3)n3ncnc(N)c23)CC1
InChIKey: YLYSDTRTAHLADP-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates. Incorporation of radioactive phosphate into the peptide substrate was determined.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 393.45, ALogP 1.55, HBA 7, HBD 3, PSA 127.3, QED 0.62
Compound (SMILES): Nc1ncnn2c(-c3ccncc3)cc(C(=O)NC3CCOCC3)c12
InChIKey: PRPDTJCUQLMLCF-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates. Incorporation of radioactive phosphate into the peptide substrate was determined.
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 338.37, ALogP 1.28, HBA 7, HBD 2, PSA 107.43, QED 0.74
Compound (SMILES): COc1cc(-c2cc(C(=O)N[C@H]3CC[C@H](NC(=O)CC(C)(C)O)CC3)c3c(N)ncnn23)ccn1
InChIKey: RSUKGEFPNMGBOB-WKILWMFISA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates. Incorporation of radioactive phosphate into the peptide substrate was determined.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 481.56, ALogP 1.7, HBA 9, HBD 4, PSA 156.76, QED 0.4
Compound (SMILES): COc1cc(-c2cc(C(=O)N[C@H]3CC[C@H](NC(=O)C4(CN)CC4)CC3)c3c(N)ncnn23)ccn1
InChIKey: STJFOQNHYGBJMM-WKILWMFISA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates. Incorporation of radioactive phosphate into the peptide substrate was determined.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 478.56, ALogP 1.28, HBA 9, HBD 4, PSA 162.55, QED 0.39
Compound (SMILES): COc1cc(-c2cc(C(=O)N[C@@H]3CCCN(C(=O)C4(N)CC4)C3)c3c(N)ncnn23)ccn1
InChIKey: DAYZSXZOOAMJOG-CQSZACIVSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates. Incorporation of radioactive phosphate into the peptide substrate was determined.
Measurement: IC50 = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 450.5, ALogP 0.59, HBA 9, HBD 3, PSA 153.76, QED 0.51
Compound (SMILES): COc1cc(-c2cc(C(=O)N[C@H]3CC[C@H](NC(=O)C(C)(C)O)CC3)c3c(N)ncnn23)ccn1
InChIKey: WLHGRZHPZGTTDT-SHTZXODSSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates. Incorporation of radioactive phosphate into the peptide substrate was determined.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 467.53, ALogP 1.31, HBA 9, HBD 4, PSA 156.76, QED 0.42
Compound (SMILES): COc1cc(-c2cc(C(=O)N[C@H]3CC[C@@H](CO)CC3)c3c(N)ncnn23)ccn1
InChIKey: QBTHRKWAMCWNPT-XBXGTLAGSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates. Incorporation of radioactive phosphate into the peptide substrate was determined.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 396.45, ALogP 1.66, HBA 8, HBD 3, PSA 127.66, QED 0.6
Compound (SMILES): COc1cc(-c2cc(C(=O)NC[C@H]3CC[C@H](O)CC3)c3c(N)ncnn23)ccn1
InChIKey: WMYHUUNEGHOXSG-MQMHXKEQSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates. Incorporation of radioactive phosphate into the peptide substrate was determined.
Measurement: IC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 396.45, ALogP 1.66, HBA 8, HBD 3, PSA 127.66, QED 0.6
Compound (SMILES): COc1cc(-c2cc(C(=O)N[C@H]3CC[C@H](C(=O)O)CC3)c3c(N)ncnn23)ccn1
InChIKey: PUCDZZSVDMHUGJ-AULYBMBSSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates. Incorporation of radioactive phosphate into the peptide substrate was determined.
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 410.43, ALogP 1.76, HBA 8, HBD 3, PSA 144.73, QED 0.58
Compound (SMILES): COc1cc(-c2cc(C(=O)N[C@H]3CCOC3)c3c(N)ncnn23)ccn1
InChIKey: UDKRCQGCIZCTBT-NSHDSACASA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates. Incorporation of radioactive phosphate into the peptide substrate was determined.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 354.37, ALogP 0.9, HBA 8, HBD 2, PSA 116.66, QED 0.71
Compound (SMILES): CCN1CCCC1CNC(=O)[C@H]1CC[C@H](NC(=O)c2cc(-c3ccnc(OC)c3)n3ncnc(N)c23)CC1
InChIKey: IOEDVCXXEWBZPB-FWNKOSSWSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Kinase Assay: The effectiveness of compounds of the present invention as inhibitors of protein kinases can be readily tested by assays known to those skilled in the art. For example, in vitro protein kinase assays may be conducted with a relevant purified protein kinase and an appropriate synthetic substrate to determine the inhibitory activity of the compounds. Assays for inhibition of CK2 by the instant compounds were performed in 384-well plates with reaction mixtures containing 10 uM of peptide substrate (RRRADDSDDDDD-NH2), [gamma-33P]ATP (10 uCi) at 25 uM (CK2A1) or 5 uM (CK2A2), 20 mM Hepes (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 0.25 mM dithiothreitol, Brij-35 at 0.015%, and recombinant CK2A1 (10 nM, Invitrogen) or CK2A2 (5 nM, Upstate Biotechnology). Reaction mixtures were incubated at 30 C. for 1 hour, and reaction products were captured by binding to phosphocellulose (P81) filter plates. Incorporation of radioactive phosphate into the peptide substrate was determined.
Measurement: IC50 = 3.9 nM (pChEMBL 8.40999984741211)
Descriptors: MW 520.64, ALogP 2.27, HBA 9, HBD 3, PSA 139.77, QED 0.41