Publications by authors named "M Koegl"
Article Synopsis
- Mutations in the KRAS protein are common in cancer, with a notable example being the G12C mutation, which has targeted treatments.
- Researchers developed a novel small molecule that can degrade many KRAS mutations, demonstrating more effective and lasting effects compared to traditional inhibition.
- Their findings showed that this approach not only effectively kills cancer cells with KRAS mutations but also spares normal cells, leading to reduction in tumors in animal models.
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 broadly applicable learnings from a KRAS hit finding campaign: While we initially identified KRAS inhibitors in a biochemical high-throughput screen, we later discovered that compound potencies were all but assay artifacts linked to metal salts interfering with KRAS AlphaScreen assay technology. The source of the apparent biochemical KRAS inhibition was ultimately traced to unavoidable palladium impurities from chemical synthesis.
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- Targeted protein degradation is a new approach in drug discovery, but the natural half-life of proteins greatly influences how effective these degraders are, and this relationship hasn’t been thoroughly studied.
- Research shows that short-lived proteins can misleadingly appear to be degraded by agents that actually halt protein synthesis, like GSPT1 degraders and cytotoxic drugs.
- The findings indicate that understanding a target protein's half-life is crucial for selecting targets and designing control experiments to validate the effectiveness of new protein degrading agents.
This study investigated spectral laser-induced fluorescence signals of dyes in fuels for automotive and aerospace applications under low temperatures and cryogenic conditions down to 183 K. For this purpose, a fluorescence chamber was developed based on cooling with liquid nitrogen. The design enabled a minimal inner chamber temperature of 153 K.
View Article and Find Full Text PDFThis study investigated a novel two-color LIF (laser-induced fluorescence) technique for thermometry in coolants relevant for electric components. In principle, this diagnostic enables thermometry in liquid flows but also a simultaneous determination of film thickness and film temperature, which is relevant, e.g.
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