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Biochemistry, Biophysics, and Structural Biology
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Full-Text Articles in Life Sciences
Pharmacodynamic Assays To Facilitate Preclinical And Clinical Development Of Pre-Mrna Splicing Modulatory Drug Candidates, Yihui Shi, Amanda S. Joyner, William Shadrick, Gustavo Palacios, Chandraiah Lagisetti, Philip M. Potter, Lidia C. Sambucetti, Stefan Stamm, Thomas R. Webb
Pharmacodynamic Assays To Facilitate Preclinical And Clinical Development Of Pre-Mrna Splicing Modulatory Drug Candidates, Yihui Shi, Amanda S. Joyner, William Shadrick, Gustavo Palacios, Chandraiah Lagisetti, Philip M. Potter, Lidia C. Sambucetti, Stefan Stamm, Thomas R. Webb
Molecular and Cellular Biochemistry Faculty Publications
The spliceosome has recently emerged as a new target for cancer chemotherapy and novel antitumor spliceosome targeted agents are under development. Here, we describe two types of novel pharmacodynamic assays that facilitate drug discovery and development of this intriguing class of innovative therapeutics; the first assay is useful for preclinical optimization of small-molecule agents that target the SF3B1 spliceosomal protein in animals, the second assay is an ex vivo validated, gel-based assay for the measurement of drug exposure in human leukocytes. The first assay utilizes a highly specific bioluminescent splicing reporter, based on the skipping of exons 4-11 of a …