The present disclosure provides pladienolide compounds, pharmaceutical compositions containing such compounds, and pladienolide compounds for use in methods of medical treatment. These compounds may be useful in the treatment of cancer, particularly cancers in which agents that target the spliceosome and mutations therein are known to be useful. Also provided herein are pladienolide compounds for use in methods of treating cancers by administering at least one pladienolide compound disclosed herein and at least one additional therapy