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Leu-PEA + TGM2i
- Development stage
- Preclinical
- Lead developer
- Sun Yat-sen University Cancer Center
- Modality
- Nanoparticles → Drug Delivery Systems, Small Molecules
- Administration
- Intravenous
01
Overview
Leu-PEA + TGM2i is an experimental nanoparticle-delivered therapeutic consisting of a transglutaminase 2 (TGM2) inhibitor encapsulated within a leucine polyester amide (Leu-PEA) drug delivery system. Developed by researchers at Sun Yat-sen University Cancer Center, this agent is designed to target leukemia stem cells (LSCs) in acute myeloid leukemia (AML), particularly those resistant to venetoclax. TGM2 is overexpressed in venetoclax-resistant AML and promotes LSC survival by mediating H3Q5ser histone modification, which enhances the expression of key mitophagy genes such as PINK1 and Parkin. By inhibiting TGM2, the drug disrupts mitochondrial homeostasis, reduces mitophagic flux, and induces mitochondrial damage, thereby eliminating LSCs. The Leu-PEA nanoparticle system is utilized to enhance bone marrow targeting and minimize systemic toxicity, showing efficacy in MLL-AF9 and patient-derived xenograft models without significant myelosuppression.
- Other names
- leucine polyester amide nanoparticle-delivered TGM2 inhibitor
02
Targets
NeuraminidaseIgA (Immunoglobulin A)TGM2 (Tissue Transglutaminase 2)
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