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.

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Glutathione S-Transferase
Function: Primarily, GSTs catalyze the conjugation of glutathione (GSH) to harmful, electrophilic substances, rendering them more water-soluble and easier to excrete.
Significance: They function in detoxification, signaling, and protecting cells against oxidative stress-induced cell death.

Structure: They often exist as dimers and are present in almost all aerobic organisms, including plants, where they are crucial for stress response.

Clinical Relevance: Genetic polymorphisms in human GSTs can alter susceptibility to cancer and inflammatory diseases. They are also associated with drug resistance in parasites.