Dirk Kessler
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View article: Discovery of Small Molecules that Bind to Son of Sevenless 2 (SOS2)
Discovery of Small Molecules that Bind to Son of Sevenless 2 (SOS2) Open
The Son of Sevenless (SOS) protein family includes two highly homologous proteins, SOS1 and SOS2, that act as guanine nucleotide exchange factors (GEFs) for RAS proteins. They catalyze the GDP-to-GTP exchange, resulting in an increase of t…
View article: A ligand discovery toolbox for the WWE domain family of human E3 ligases
A ligand discovery toolbox for the WWE domain family of human E3 ligases Open
The WWE domain is a relatively under-researched domain found in twelve human proteins and characterized by a conserved tryptophan-tryptophan-glutamate (WWE) sequence motif. Six of these WWE domain-containing proteins also contain domains w…
View article: Chasing Red Herrings: Palladium Metal Salt Impurities Feigning KRAS Activity in Biochemical Assays
Chasing Red Herrings: Palladium Metal Salt Impurities Feigning KRAS Activity in Biochemical Assays Open
Identifying promising chemical starting points for small molecule inhibitors of active, GTP-loaded KRAS "on" remains of great importance to clinical oncology and represents a significant challenge in medicinal chemistry. Here, we describe …
View article: Ligandability assessment of the C‐terminal Rel‐homology domain of NFAT1
Ligandability assessment of the C‐terminal Rel‐homology domain of NFAT1 Open
Transcription factors are generally considered challenging, if not “undruggable”, targets but they promise new therapeutic options due to their fundamental involvement in many diseases. In this study, we aim to assess the ligandability of …
View article: CD-20-0142R1_Supplementary_Figures_S1-S5.docx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition
CD-20-0142R1_Supplementary_Figures_S1-S5.docx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Open
Supplementary Figures S1-S5
View article: Supplementary Materials and Methods, Tables S1 through S3 and Figures S1 and S2 from BI 885578, a Novel IGF1R/INSR Tyrosine Kinase Inhibitor with Pharmacokinetic Properties That Dissociate Antitumor Efficacy and Perturbation of Glucose Homeostasis
Supplementary Materials and Methods, Tables S1 through S3 and Figures S1 and S2 from BI 885578, a Novel IGF1R/INSR Tyrosine Kinase Inhibitor with Pharmacokinetic Properties That Dissociate Antitumor Efficacy and Perturbation of Glucose Homeostasis Open
Supplementary Materials and Methods, Tables S1 through S3 and Figures S1 and S2 - Supplementary Materials and Methods: The sources, application and dilution of the antibodies used for Western blotting (WB) and immunohistochemical (IHC) ana…
View article: Supplementary Materials and Methods, Tables S1 through S3 and Figures S1 and S2 from BI 885578, a Novel IGF1R/INSR Tyrosine Kinase Inhibitor with Pharmacokinetic Properties That Dissociate Antitumor Efficacy and Perturbation of Glucose Homeostasis
Supplementary Materials and Methods, Tables S1 through S3 and Figures S1 and S2 from BI 885578, a Novel IGF1R/INSR Tyrosine Kinase Inhibitor with Pharmacokinetic Properties That Dissociate Antitumor Efficacy and Perturbation of Glucose Homeostasis Open
Supplementary Materials and Methods, Tables S1 through S3 and Figures S1 and S2 - Supplementary Materials and Methods: The sources, application and dilution of the antibodies used for Western blotting (WB) and immunohistochemical (IHC) ana…
View article: Data from BI 885578, a Novel IGF1R/INSR Tyrosine Kinase Inhibitor with Pharmacokinetic Properties That Dissociate Antitumor Efficacy and Perturbation of Glucose Homeostasis
Data from BI 885578, a Novel IGF1R/INSR Tyrosine Kinase Inhibitor with Pharmacokinetic Properties That Dissociate Antitumor Efficacy and Perturbation of Glucose Homeostasis Open
Inhibition of the IGF1R, INSRA, and INSRB receptor tyrosine kinases represents an attractive approach of pharmacologic intervention in cancer, owing to the roles of the IGF1R and INSRA in promoting cell proliferation and survival. However,…
View article: Data from BI 885578, a Novel IGF1R/INSR Tyrosine Kinase Inhibitor with Pharmacokinetic Properties That Dissociate Antitumor Efficacy and Perturbation of Glucose Homeostasis
Data from BI 885578, a Novel IGF1R/INSR Tyrosine Kinase Inhibitor with Pharmacokinetic Properties That Dissociate Antitumor Efficacy and Perturbation of Glucose Homeostasis Open
Inhibition of the IGF1R, INSRA, and INSRB receptor tyrosine kinases represents an attractive approach of pharmacologic intervention in cancer, owing to the roles of the IGF1R and INSRA in promoting cell proliferation and survival. However,…
View article: CD-20-0142R1_Supplementary_Table_S5.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition
CD-20-0142R1_Supplementary_Table_S5.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Open
Table S5
View article: CD-20-0142R1_Supplementary_Table_S2.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition
CD-20-0142R1_Supplementary_Table_S2.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Open
Table S2
View article: Data from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition
Data from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Open
KRAS is the most frequently mutated driver of pancreatic, colorectal, and non–small cell lung cancers. Direct KRAS blockade has proved challenging, and inhibition of a key downstream effector pathway, the RAF–MEK–ERK cascade, has shown lim…
View article: CD-20-0142R1_Supplementary_Table_S2.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition
CD-20-0142R1_Supplementary_Table_S2.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Open
Table S2
View article: CD-20-0142R1_Supplementary_Table_S4.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition
CD-20-0142R1_Supplementary_Table_S4.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Open
Table S4
View article: Data from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition
Data from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Open
KRAS is the most frequently mutated driver of pancreatic, colorectal, and non–small cell lung cancers. Direct KRAS blockade has proved challenging, and inhibition of a key downstream effector pathway, the RAF–MEK–ERK cascade, has shown lim…
View article: CD-20-0142R1_Supplementary_Table_S4.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition
CD-20-0142R1_Supplementary_Table_S4.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Open
Table S4
View article: CD-20-0142R1_Supplementary_Table_S9.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition
CD-20-0142R1_Supplementary_Table_S9.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Open
Table S9
View article: CD-20-0142R1_Supplementary_Table_S7.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition
CD-20-0142R1_Supplementary_Table_S7.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Open
Table S7
View article: CD-20-0142R1_Supplementary_Table_S5.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition
CD-20-0142R1_Supplementary_Table_S5.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Open
Table S5
View article: CD-20-0142R1_Supplementary_Figures_S1-S5.docx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition
CD-20-0142R1_Supplementary_Figures_S1-S5.docx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Open
Supplementary Figures S1-S5
View article: CD-20-0142R1_Supplementary_Tables.docx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition
CD-20-0142R1_Supplementary_Tables.docx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Open
Supplementary Data, Table S1, S3, S6, S8, S10-S13
View article: CD-20-0142R1_Supplementary_Table_S9.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition
CD-20-0142R1_Supplementary_Table_S9.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Open
Table S9
View article: CD-20-0142R1_Supplementary_Tables.docx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition
CD-20-0142R1_Supplementary_Tables.docx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Open
Supplementary Data, Table S1, S3, S6, S8, S10-S13
View article: CD-20-0142R1_Supplementary_Table_S7.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition
CD-20-0142R1_Supplementary_Table_S7.xlsx from BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition Open
Table S7
View article: Fragment Optimization of Reversible Binding to the Switch II Pocket on KRAS Leads to a Potent, In Vivo Active KRAS <sup>G12C</sup> Inhibitor
Fragment Optimization of Reversible Binding to the Switch II Pocket on KRAS Leads to a Potent, In Vivo Active KRAS <sup>G12C</sup> Inhibitor Open
Activating mutations in KRAS are the most frequent oncogenic alterations in cancer. The oncogenic hotspot position 12, located at the lip of the switch II pocket, offers a covalent attachment point for KRASG12C inhibitors. To date, KRASG12…
View article: Front Cover: Getting a Grip on the Undrugged: Targeting β‐Catenin with Fragment‐Based Methods (9/2021)
Front Cover: Getting a Grip on the Undrugged: Targeting β‐Catenin with Fragment‐Based Methods (9/2021) Open
The Front Cover shows the discovered fragment in the process of binding to β-catenin bound to the transcription factor TCF4 and co-activator BCL9 (PDB ID: 2GL7). The electron density surrounding the ligand and the chemical shift perturbati…
View article: Targeting Son of Sevenless 1: The pacemaker of KRAS
Targeting Son of Sevenless 1: The pacemaker of KRAS Open
Son of Sevenless (SOS) is a guanine nucleotide exchange factor that activates the important cell signaling switch KRAS. SOS acts as a pacemaker for KRAS, the beating heart of cancer, by catalyzing the "beating" from the KRAS(off) to the KR…
View article: One Atom Makes All the Difference: Getting a Foot in the Door between SOS1 and KRAS
One Atom Makes All the Difference: Getting a Foot in the Door between SOS1 and KRAS Open
KRAS, the most common oncogenic driver in human cancers, is controlled and signals primarily through protein-protein interactions (PPIs). The interaction between KRAS and SOS1, crucial for the activation of KRAS, is a typical, challenging …