lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Fc1ccc(-c2cn3ccnc3nc2-c2ccc(CN3CCC(c4n[nH]c(-c5cnccn5)n4)CC3)cc2)cc1
InChIKey: WOIBNSMAQNNKOE-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 186 nM (pChEMBL 6.730000019073486)
Descriptors: MW 531.6, ALogP 5.16, HBA 8, HBD 1, PSA 100.78, QED 0.32
Compound (SMILES): Cc1cccc(-c2nc(C3CCN(Cc4ccc(-c5nc6ncc(Br)n6cc5-c5ccc(F)cc5)cc4)CC3)n[nH]2)n1
InChIKey: XXMDMGCWKMTCOF-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 623.53, ALogP 6.83, HBA 7, HBD 1, PSA 87.89, QED 0.22
Compound (SMILES): Fc1ccc(-c2cn3c(Cl)cnc3nc2-c2ccc(CN3CCC(c4n[nH]c(-c5ccccn5)n4)CC3)cc2)cc1
InChIKey: DCGNAWAKDKLBPU-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 565.06, ALogP 6.42, HBA 7, HBD 1, PSA 87.89, QED 0.25
Compound (SMILES): Cc1cccc(-c2nc(C3CCN(Cc4ccc(-c5nc6nccn6cc5-c5ccccc5F)cc4)CC3)n[nH]2)n1
InChIKey: FUCRZGNUVYOQLJ-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 544.64, ALogP 6.07, HBA 7, HBD 1, PSA 87.89, QED 0.27
Compound (SMILES): Brc1cnc2nc(-c3ccc(CN4CC(c5n[nH]c(-c6ccccn6)n5)C4)cc3)c(-c3ccccc3)cn12
InChIKey: YUJQWKDHWHVRHF-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 563.46, ALogP 5.61, HBA 7, HBD 1, PSA 87.89, QED 0.28
Compound (SMILES): Cc1cn2cc(-c3ccccc3)c(-c3ccc(CN4CC(c5n[nH]c(-c6ccccn6)n5)C4)cc3)nc2n1
InChIKey: SOHHGORZHYEGRX-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 498.59, ALogP 5.15, HBA 7, HBD 1, PSA 87.89, QED 0.34
Compound (SMILES): Cc1cccc(-c2nc(C3CN(Cc4ccc(-c5nc6nc(C)c(Br)n6cc5-c5ccccc5)cc4)C3)n[nH]2)n1
InChIKey: AWYGAVYSWRPYNI-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 591.52, ALogP 6.22, HBA 7, HBD 1, PSA 87.89, QED 0.25
Compound (SMILES): CNc1c(-c2ccccc2)c(-c2ccc(CN3CC(c4n[nH]c(-c5ccccn5)n4)C3)cc2)nc2nccn12
InChIKey: HAYWLTZXUNDCPW-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 513.61, ALogP 4.88, HBA 8, HBD 2, PSA 99.92, QED 0.31
Compound (SMILES): CNc1c(-c2ccccc2)c(-c2ccc(CN3CC(c4n[nH]c(-c5ccccn5)n4)C3)cc2)nc2ncc(Br)n12
InChIKey: OEULVKFFXFWPQV-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 592.51, ALogP 5.65, HBA 8, HBD 2, PSA 99.92, QED 0.25
Compound (SMILES): CNc1c(-c2ccccc2)c(-c2ccc(CN3CC(c4n[nH]c(-c5ccccn5)n4)C3)cc2)nc2nc(C)cn12
InChIKey: LFRPXRBPJQZTMI-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 527.64, ALogP 5.19, HBA 8, HBD 2, PSA 99.92, QED 0.29
Compound (SMILES): CNc1c(-c2ccccc2)c(-c2ccc(CN3CC(c4n[nH]c(-c5cccc(C)n5)n4)C3)cc2)nc2nc(C)cn12
InChIKey: ONLWOOCHZYUXQV-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 541.66, ALogP 5.5, HBA 8, HBD 2, PSA 99.92, QED 0.28
Compound (SMILES): COc1nn2cc(-c3c(F)cccc3F)c(-c3ccc(CN4CC(c5n[nH]c(-c6ccccn6)n5)C4)cc3)nc2c1CO
InChIKey: POMKNVSPIRVORC-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 580.6, ALogP 4.62, HBA 9, HBD 2, PSA 117.35, QED 0.27
Compound (SMILES): COc1nn2cc(-c3c(F)cccc3F)c(-c3ccc(CN4CC(c5n[nH]c(-c6cccc(C)n6)n5)C4)cc3)nc2c1CO
InChIKey: COHKELNFIIQCIB-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 594.63, ALogP 4.93, HBA 9, HBD 2, PSA 117.35, QED 0.25
Compound (SMILES): COc1nn2cc(-c3c(F)cccc3F)c(-c3ccc(CN4CCC(c5n[nH]c(-c6cccc(C)n6)n5)CC4)cc3)nc2c1CO
InChIKey: PMSNOSRKBKEZFA-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 622.68, ALogP 5.71, HBA 9, HBD 2, PSA 117.35, QED 0.22
Compound (SMILES): COc1nn2cc(-c3c(F)cccc3F)c(-c3ccc(CN4CCC(c5n[nH]c(-c6ccccn6)n5)CC4)cc3)nc2c1CO
InChIKey: WYKHGGZTSNAFCH-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 608.65, ALogP 5.4, HBA 9, HBD 2, PSA 117.35, QED 0.24
Compound (SMILES): Cc1cn2c(NC(C)C)c(-c3ccccc3)c(-c3ccc(CN4CC(c5n[nH]c(-c6ccccn6)n5)C4)cc3)nc2n1
InChIKey: KUPCIMLXVLSZBL-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 555.69, ALogP 5.97, HBA 8, HBD 2, PSA 99.92, QED 0.24
Compound (SMILES): Cc1cccc(-c2nc(C3CN(Cc4ccc(-c5nc6nc(C)cn6c(NC(C)C)c5-c5ccccc5)cc4)C3)n[nH]2)n1
InChIKey: TZOOLGKFXCYWIR-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 569.72, ALogP 6.28, HBA 8, HBD 2, PSA 99.92, QED 0.22
Compound (SMILES): CC(C)Nc1c(-c2ccccc2)c(-c2ccc(CN3CC(c4n[nH]c(-c5ccccn5)n4)C3)cc2)nc2nccn12
InChIKey: JWAAHLMUTIVCTN-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 541.66, ALogP 5.66, HBA 8, HBD 2, PSA 99.92, QED 0.26
Compound (SMILES): CNc1c(-c2ccccc2)c(-c2ccc(CN3CC(c4n[nH]c(-c5ccccn5)n4)C3)cc2)nc2nc(-c3ccccn3)nn12
InChIKey: KXBWZMRHGBHBBY-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 591.68, ALogP 5.34, HBA 10, HBD 2, PSA 125.7, QED 0.24
Compound (SMILES): CC(C)Nc1c(-c2ccccc2)c(-c2ccc(CN3CC(c4n[nH]c(-c5ccccn5)n4)C3)cc2)nc2nc(-c3ccccn3)nn12
InChIKey: UYRKFMAPPBMERN-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 619.74, ALogP 6.12, HBA 10, HBD 2, PSA 125.7, QED 0.2
Compound (SMILES): Cc1cccc(-c2nc(C3CN(Cc4ccc(-c5nc6nc(-c7ccccn7)nn6c(NC(C)C)c5-c5ccccc5)cc4)C3)n[nH]2)n1
InChIKey: YDQGQHBPNSJCQU-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 633.76, ALogP 6.43, HBA 10, HBD 2, PSA 125.7, QED 0.19
Compound (SMILES): c1ccc(-c2cn3nc(C4CC4)nc3nc2-c2ccc(CN3CC(c4n[nH]c(-c5ccccn5)n4)C3)cc2)cc1
InChIKey: KCWSEQZHIICHPH-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 525.62, ALogP 5.12, HBA 8, HBD 1, PSA 100.78, QED 0.31
Compound (SMILES): CSc1nc2nc(-c3ccc(CN4CC(c5n[nH]c(-c6cccc(C)n6)n5)C4)cc3)c(-c3ccccc3)cn2n1
InChIKey: BANWNETXRJVKLD-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 545.68, ALogP 5.27, HBA 9, HBD 1, PSA 100.78, QED 0.27
Compound (SMILES): CSc1nc2nc(-c3ccc(CN4CC(c5n[nH]c(-c6ccccn6)n5)C4)cc3)c(-c3ccccc3)cn2n1
InChIKey: KXVGDOGLFUKMBR-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 531.65, ALogP 4.96, HBA 9, HBD 1, PSA 100.78, QED 0.29
Compound (SMILES): CSc1nc2nc(-c3ccc(CN4CCC(c5n[nH]c(-c6ccccn6)n5)CC4)cc3)c(-c3ccccc3)cn2n1
InChIKey: WLXXUZBRYVKCGM-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 559.7, ALogP 5.74, HBA 9, HBD 1, PSA 100.78, QED 0.25
Compound (SMILES): CSc1nc2nc(-c3ccc(CN4CCC(c5n[nH]c(-c6ncccn6)n5)CC4)cc3)c(-c3ccccc3)cn2n1
InChIKey: UWVKVXDDBDYZSR-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 560.69, ALogP 5.13, HBA 10, HBD 1, PSA 113.67, QED 0.27
Compound (SMILES): CSc1nc2nc(-c3ccc(CN4CCC(c5n[nH]c(-c6cnccn6)n5)CC4)cc3)c(-c3ccccc3)cn2n1
InChIKey: SEIIYUCYULPFJQ-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 560.69, ALogP 5.13, HBA 10, HBD 1, PSA 113.67, QED 0.27
Compound (SMILES): CSc1nc2nc(-c3ccc(CN4CCC(c5n[nH]c(-c6cccc(C)n6)n5)CC4)cc3)c(-c3ccccc3)cn2n1
InChIKey: ZUILYPNRYTWPOX-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 573.73, ALogP 6.05, HBA 9, HBD 1, PSA 100.78, QED 0.23
Compound (SMILES): CS(=O)(=O)c1nc2nc(-c3ccc(CN4CCC(c5n[nH]c(-c6ccccn6)n5)CC4)cc3)c(-c3ccccc3)cn2n1
InChIKey: KHSLMVKNPXOWDM-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 591.7, ALogP 4.42, HBA 10, HBD 1, PSA 134.92, QED 0.29
Compound (SMILES): COC(=O)c1cn2cc(-c3ccccc3)c(-c3ccc(CN4CC(c5n[nH]c(-c6cccc(C)n6)n5)C4)cc3)nc2n1
InChIKey: GBFJUXFRUIRHLW-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 556.63, ALogP 4.94, HBA 9, HBD 1, PSA 114.19, QED 0.28
Compound (SMILES): COC(=O)c1cn2cc(-c3ccccc3)c(-c3ccc(CN4CC(c5n[nH]c(-c6ccccn6)n5)C4)cc3)nc2n1
InChIKey: GCFYFGLETUUVLJ-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 542.6, ALogP 4.63, HBA 9, HBD 1, PSA 114.19, QED 0.29
Compound (SMILES): OCc1cn2cc(-c3ccccc3)c(-c3ccc(CN4CC(c5n[nH]c(-c6ccccn6)n5)C4)cc3)nc2n1
InChIKey: XUMQVWJMCUIXNH-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 514.59, ALogP 4.34, HBA 8, HBD 2, PSA 108.12, QED 0.33
Compound (SMILES): Cc1nc2nc(-c3ccc(CN4CCC(c5n[nH]c(-c6ccccn6)n5)CC4)cc3)c(-c3cc(F)ccc3F)cn2n1
InChIKey: NHYJWBOVHHADEN-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 563.62, ALogP 5.6, HBA 8, HBD 1, PSA 100.78, QED 0.28
Compound (SMILES): OCc1cnn2cc(-c3c(F)cccc3F)c(-c3ccc(CN4CC(c5n[nH]c(-c6ccccn6)n5)C4)cc3)nc12
InChIKey: NKFREIUXOLOXHW-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: TR-FRET Assay: Akt1 inhibitory activity of compounds of the present invention may be quantified0 employing the Akt1 TR-FRET assay as described in the following paragraphs. His-tagged human recombinant kinase full-length Akt1 expressed in insect cells was purchased form Invitrogen (part number PV 3599). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in am- ide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany).For the assay 50 nl of a IOOfold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (Greiner Bio- One, Frickenhausen, Germany), 2 ul of a solution of Akt1 in assay buffer [50 mM TRIS/HCI pH 7.5, 5 mM MgCI2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22C to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 550.57, ALogP 4.61, HBA 8, HBD 2, PSA 108.12, QED 0.3
Compound (SMILES): C[C@H](Nc1nccc(N2C(=O)OC(C)(C)[C@@H]2c2ccccc2)n1)c1ccccc1
InChIKey: QTNNXCXGAWXJSN-JXFKEZNVSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: LC-MS Biochemical Assay: Mutant IDH1 R132H catalytic activity was monitored using the quantitative liquid chromatography/mass spectrometry (LC-MS) detection of 2-HG, a product of the NADPH-dependent alpha-KG reduction reaction.More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Costar, Cat. No. 781201) using a final reaction volume of 30 uL and the following assay buffer conditions: 50 mM HEPES pH 7.4, 10 mM MgCl2, 50 mM KCl, 1 mM DTT, 0.02% BSA, 5 uM NADPH and 100 uM alpha-KG.The final reaction mixture contained 3.3% DMSO and inhibitors with concentrations ranging 0.02-50 uM. The IDH1 enzyme was used at a final concentration of 0.25 nM. Following 45 minutes incubation, the reaction mixtures were quenched by the addition of 10 uL of 16% formic acid containing 800 nM of 5-carbon labeled 13C-2-HG). The protein was then precipitated by the addition of 2.5 volumes of acetonitrile followed by centrifugation (3000xg, 20 minutes).
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 388.47, ALogP 5.13, HBA 5, HBD 1, PSA 67.35, QED 0.66
Compound (SMILES): CC(Nc1nccc(N2CCOC2=O)n1)c1ccccc1
InChIKey: VRCPPSXFONHTQP-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: LC-MS Biochemical Assay: Mutant IDH1 R132H catalytic activity was monitored using the quantitative liquid chromatography/mass spectrometry (LC-MS) detection of 2-HG, a product of the NADPH-dependent alpha-KG reduction reaction.More specifically, the biochemical reactions were performed at room temperature in 384-well Greiner flat-bottom plates (Costar, Cat. No. 781201) using a final reaction volume of 30 uL and the following assay buffer conditions: 50 mM HEPES pH 7.4, 10 mM MgCl2, 50 mM KCl, 1 mM DTT, 0.02% BSA, 5 uM NADPH and 100 uM alpha-KG.The final reaction mixture contained 3.3% DMSO and inhibitors with concentrations ranging 0.02-50 uM. The IDH1 enzyme was used at a final concentration of 0.25 nM. Following 45 minutes incubation, the reaction mixtures were quenched by the addition of 10 uL of 16% formic acid containing 800 nM of 5-carbon labeled 13C-2-HG). The protein was then precipitated by the addition of 2.5 volumes of acetonitrile followed by centrifugation (3000xg, 20 minutes).
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 284.32, ALogP 2.61, HBA 5, HBD 1, PSA 67.35, QED 0.93