MYB (c-Myb transcription factor) mRNA

Class

Small molecule mRNA degrader

Pathway

MYB oncogenic transcriptional program

MYB (c-Myb) is a transcription factor, a protein that binds DNA and switches on genes controlling cell proliferation, differentiation, and survival. It is essential during normal blood cell development, but in several cancers, MYB becomes abnormally activated, either through chromosomal rearrangements or increased expression, driving a self-reinforcing program of unchecked growth. This makes MYB an attractive target in malignancies such as adenoid cystic carcinoma and certain leukemias, where the tumor’s survival is closely tied to sustained MYB activity. Transcription factors like MYB lack the deep, well-defined pockets that most small-molecule drugs need to bind and block, making them historically difficult to inhibit directly. One strategy to circumvent this is to reduce the transcription factor at its source, by promoting the degradation of the messenger RNA (mRNA) that carries the instructions for building the MYB protein, before it can be translated. Lowering mRNA levels lowers protein levels, dampening the oncogenic transcriptional program that MYB sustains. This mRNA-degrading approach represents a distinct pharmacological modality from conventional enzyme inhibitors or antibodies, and is being explored broadly as a way to reach targets previously considered undruggable.