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beta-lapachone + RSL-3
- Development stage
- Preclinical
- Lead developer
- Chinese Academy of Medical Sciences
- Modality
- Small Molecules, Nanoparticles → Drug Delivery Systems
- Administration
- Intravenous
01
Overview
beta-lapachone + RSL-3 is a synergistic combination of the bioactivatable quinone beta-lapachone and the GPX4 inhibitor RSL-3. Beta-lapachone is bioactivated by NAD(P)H:quinone oxidoreductase 1 (NQO1), triggering a futile redox cycle that generates high levels of reactive oxygen species (ROS) and oxidative stress. RSL-3 is a small molecule that covalently binds and inhibits glutathione peroxidase 4 (GPX4), a key antioxidant enzyme that prevents lipid peroxidation. By combining these two agents, the formulation simultaneously drives ROS generation and blocks the cell's primary lipid peroxide clearance mechanism, leading to robust induction of ferroptosis and immunogenic cell death (ICD). This combination has been investigated in preclinical models of advanced prostate cancer, particularly when co-encapsulated in a dual-targeting, ROS-responsive polymeric nanoplatform (NP@beta-Lap/RSL-3) designed to enhance tumor-specific delivery and synergize with immune checkpoint inhibitors like anti-PD-1 antibodies.
- Other names
- NP@beta-Lap/RSL-3NP@β-Lap/RSL-3beta-lapachone + RSL-3beta-lapachone and RSL-3beta-lapachone/RSL-3β-lapachone + RSL-3β-lapachone and RSL-3β-lapachone/RSL-3
02
Targets
TOP1 (DNA Topoisomerase I)GPX4 (Glutathione peroxidase 4)IDO1 (Indoleamine 2,3-dioxygenase 1)NQO1
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