Spliceosome Inhibitor

About

Challenge The newly discovered thailanstatin family of natural products exhibit potent antiproliferative activities in various human cancer cell lines. Derived from bacteria, they fight cancer by inhibiting the spliceosome, the cellular machinery that edits mRNA after transcription from DNA. The most potent member of this family, thailanstatin A is considered a natural product candidate for anticancer drug development. Despite its promising therapeutic potential, complete pharmacological characterization of thailanstatin A and development of new analogues remains hampered by limited access to this system from natural sources. In addition, a commercially viable synthetic route to prepare thailanstatin A and related compounds is currently unavailable. Solution Rice researchers have devised an optimized synthetic route to thailanstatin A and its analogues. The total synthesis of thailanstatin A has been accomplished in a linear sequence of nine steps from readily available starting materials. The high convergency of this method allows for preparation of thailanstatin A and new analogues that are useful by themselves for anticancer drug development or as payloads in antibody-drug conjugates for targeted drug delivery. Benefits and Features Rapid and efficient synthesis of anticancer natural product thailanstatin A and its congeners New chemical route that allows creation of a library of functionalized thailanstatin derivatives in quantities large enough for complete biological assessment Market Potential / Applications Cancer is a leading cause of disease globally. According to the American Cancer Society, in 2016, there will be an estimated 1,685,210 new cancer cases diagnosed and 595,690 cancer deaths in the U.S. alone. The synthetic method developed in this invention is useful for preparing anticancer natural product thailanstatin A and its variants to support cancer drug discovery programs.