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Design, Structure Optimization, and Preclinical Characterization of JAB-21822, a Covalent Inhibitor of KRAS.
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Chief executive officer, Jacobio Pharmaceuticals Group Co., Ltd., Beijing100176, P. R. China.
KRAS is the most frequently mutated driver oncogene in human cancer, and KRAS mutation is commonly found in non-small-cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). Inhibitors that covalently modify the mutated codon 12 cysteine have completed proof-of-concept studies in the clinic. Here, we describe structure-based design and cocrystal-aided drug optimization of a series of compounds with the 1,8-naphthyridine-3-carbonitrile scaffold.
View Article and Find Full Text PDFCloning a Chloroplast Genome in and .
Bio Protoc
January 2025
Biochemistry Department, Western University, London, Canada.
Chloroplast genomes present an alternative strategy for large-scale engineering of photosynthetic eukaryotes. Prior to our work, the chloroplast genomes of (204 kb) and (140 kb) had been cloned using bacterial and yeast artificial chromosome (BAC/YAC) libraries, respectively. These methods lack design flexibility as they are reliant upon the random capture of genomic fragments during BAC/YAC library creation; additionally, both demonstrated a low efficiency (≤ 10%) for correct assembly of the genome in yeast.
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Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
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