Menin / DOT1L
Epigenetic Proteins
Revumenib (B1, Polyphenol)
Pinometostat (Thiazole)
Menin and DOT1L are critical cofactors in MLL-rearranged (MLL-r) leukemias, where their combined inhibition acts synergistically to trigger leukemia cell differentiation and apoptosis by disrupting the MLL-fusion protein complex on chromatin. Menin inhibitors (revumenib) block Menin-KMT2A binding, while DOT1L inhibitors (pinometostat) target the H3K79 methyltransferase, both suppressing key target genes like HOXA9 and MEIS1.