Dual targeting of GPX4 and TXNRD1 triggers eradication of AML cells through induction of apoptosis and ferroptosis - PubMed
6 hours ago
- #AML Treatment
- #Ferroptosis Induction
- #GPX4 Inhibition
- Two novel compounds, HA344 and #231, target both ferroptosis and apoptosis pathways to effectively eradicate MDS/AML cell lines and patient-derived bone-marrow blasts.
- Primary targets of these compounds are glutathione peroxidase 4 (GPX4) and thioredoxin reductase 1 (TXNRD1), inhibiting them in the micromolar range.
- HA344 and #231 show a higher affinity for selenium-containing GPX4 (GPX4-Se) compared to sulfur-containing GPX4 (GPX4-S), confirming their potential as covalent inhibitors.
- This dual targeting strategy offers a promising new therapeutic approach for treating MDS/AML, addressing the limited efficacy of current treatments.