Precursor messenger RNA (pre-mRNA) splicing is a fundamental process in gene expression and is the key to the pathology of numerous diseases, including cancer. Splicing deficits may affect the ability of cells to proliferate, and certain splicing isoforms have been found to act as drivers of cancer. Recently, potent antitumor natural products such as FR901464 have been discovered to trigger apoptosis in cells by inhibiting pre-mRNA splicing, thus affecting mRNA levels of oncogenes. Although potent, these natural anti-tumor agents are difficult to synthesize, hindering the potential of these molecules as ideal anticancer drug candidates.
Description
Researchers are exploring improved methodology for preparing and synthesizing these compounds and their analogs in easy ways. Additionally, certain synthetic analogs of these natural products have been demonstrated to possess a multi-fold increase in antitumor activity as compared to their natural parent molecule. Researchers at the University of Pittsburgh have synthesized novel analogs of the antitumor compound FR901464 that show much higher antitumor activity with an easier and more efficient means of synthesis. Three of these analogs are very stable and show antiproliferative activity against various cancer cell lines and multidrug-resistant cells in the picomolar range.
Applications
· Treating cancer
Advantages
· Increased antitumor activity compared to naturally occurring parent compound
· Easier to synthesize
Invention Readiness
In vivo data
IP Status
https://patents.google.com/patent/US7825267B2/en; https://patents.google.com/patent/US8309599B2/en; https://patents.google.com/patent/US9771377B2/en
