Jeffrey S. Iwig
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View article: Effects of CT-388, a once-weekly signaling-biased dual GLP-1/GIP receptor agonist, on weight loss and glycemic control in preclinical models and participants with obesity
Effects of CT-388, a once-weekly signaling-biased dual GLP-1/GIP receptor agonist, on weight loss and glycemic control in preclinical models and participants with obesity Open
Biased agonism of the glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptors (GLP-1R/GIPR) yields greater weight loss and better glycemic control than unbiased agonism in preclinical models. To evaluate whether bias…
View article: Catalytic degradation of circulating targets with FcRn-mediated cycling LYTACs
Catalytic degradation of circulating targets with FcRn-mediated cycling LYTACs Open
Circulating proteins are common targets for the discovery of occupancy-based inhibitors including monoclonal antibodies. Effective inhibition of target pathogenicity with blocking approaches, however, is often challenged by target paramete…
View article: Discovery of <i>N</i>-(1-Acryloylazetidin-3-yl)-2-(1<i>H</i>-indol-1-yl)acetamides as Covalent Inhibitors of KRAS<sup>G12C</sup>
Discovery of <i>N</i>-(1-Acryloylazetidin-3-yl)-2-(1<i>H</i>-indol-1-yl)acetamides as Covalent Inhibitors of KRAS<sup>G12C</sup> Open
KRAS regulates many cellular processes including proliferation, survival, and differentiation. Point mutants of KRAS have long been known to be molecular drivers of cancer. KRAS p.G12C, which occurs in approximately 14% of lung adenocarcin…
View article: A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1
A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1 Open
RasGRPs are guanine nucleotide exchange factors that are specific for Ras or Rap, and are important regulators of cellular signaling. Aberrant expression or mutation of RasGRPs results in disease. An analysis of RasGRP1 SNP variants led to…
View article: Author response: A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1
Author response: A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1 Open
Article Figures and data Abstract eLife digest Introduction Results and discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract RasGRPs are guanine nucle…
View article: The mechanism of a formaldehyde-sensing transcriptional regulator
The mechanism of a formaldehyde-sensing transcriptional regulator Open
Most organisms are exposed to the genotoxic chemical formaldehyde, either from endogenous or environmental sources. Therefore, biology has evolved systems to perceive and detoxify formaldehyde. The frmRA(B) operon that is present in many b…
View article: Monitoring the Waiting Time Sequence of Single Ras GTPase Activation Events Using Liposome Functionalized Zero-Mode Waveguides
Monitoring the Waiting Time Sequence of Single Ras GTPase Activation Events Using Liposome Functionalized Zero-Mode Waveguides Open
Activation of small GTPases of the Ras superfamily by guanine nucleotide exchange factors (GEFs) is a key step in numerous cell signaling processes. Unveiling the detailed molecular mechanisms of GEF-GTPase signaling interactions is of gre…