Induced Modification And Degradation Of Intracellular Proteins In Lysosomes: Methylarginine Targeting Chimera (MrTAC)

Brief Description

A revolutionary drug modality for the selective modification and degradation of intracellular proteins in lysosomes.

Full Description

Methylarginine Targeting Chimera (MrTAC) is a heterobifunctional small molecule designed to selectively induce arginine methylation, facilitating the targeted degradation of intracellular proteins within lysosomes. This innovative approach leverages the enzyme protein arginine N-methyltransferase 1 (PRMT1) to chemically modify proteins, directing them towards lysosomal degradation, a pathway previously underutilized in targeted protein degradation therapies.

Suggested uses

• Targeted cancer therapies by degrading disease-causing proteins overexpressed in cancer cells. 
• Drug development for diseases associated with protein dysregulation and mutation. 
• Research tools for studying protein function and methylation effects on cell biology

Advantages

• High selectivity in targeting specific proteins for degradation without affecting global methylation patterns. 
• Utilizes the lysosomal degradation pathway, offering an alternative to proteasomal degradation. 
• Capable of degrading proteins across various cell lines, timescales, and doses. 
• Drives biological loss-of-function phenotypes affecting survival, transcription, and proliferation. 
• Overcomes challenges associated with proteasomal targeting, such as ineffective ubiquitination and protein mutation.

Patent Status

Patent Pending

Related Materials

• Seabrook, L. J., et al. Albrecht, L. V. (2024). Methylarginine targeting chimeras for lysosomal degradation of intracellular proteins. Nat. Chem. Biol. 20.
• Seabrook, L. J., Albrecht, L. V. (2024). Targeting proteins to lysosomes with a chemical inducer of arginine methylation. Nat. Chem. Biol. 20.