Structurally-Diverse Non-Covalent Allosteric KRAS Inhibitors Structurally Diverse Non-Covalent Allosteric KRAS Inhibitors
نویسندگان
چکیده
منابع مشابه
A quantitative systems pharmacology analysis of KRAS G12C covalent inhibitors
The KRAS oncogene is the most common, activating, oncogenic mutation in human cancer. KRAS has proven difficult to target effectively. Two different strategies have recently been described for covalently targeting the most common activating KRAS mutant in lung cancer, KRAS G12C. Previously, we have developed a computational model of the processes that regulate Ras activation and this model has ...
متن کاملPotent and Selective Covalent Quinazoline Inhibitors of KRAS G12C.
Targeted covalent small molecules have shown promise for cancers driven by KRAS G12C. Allosteric compounds that access an inducible pocket formed by movement of a dynamic structural element in KRAS, switch II, have been reported, but these compounds require further optimization to enable their advancement into clinical development. We demonstrate that covalent quinazoline-based switch II pocket...
متن کاملQuantitative Systems Pharmacology Analysis of KRAS G12C Covalent Inhibitors.
KRAS has proven difficult to target pharmacologically. Two strategies have recently been described for covalently targeting the most common KRAS mutant in lung cancer, KRAS G12C. Previously, we developed a computational model of the processes that regulate Ras activation. Here, we use this model to investigate KRAS G12C covalent inhibitors. We updated the model to include Ras protein turnover, ...
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ژورنال
عنوان ژورنال: Biophysical Journal
سال: 2020
ISSN: 0006-3495
DOI: 10.1016/j.bpj.2019.11.1820