Novel iron-mediated cell death (Ferroptosis) inducer, HSB-1216, suppress acute myeloid leukemia growth

Acute myeloid leukemia (AML) is a heterogeneous and intrinsically resistant stem cell neoplasm, occurring in about 14 000 patients the US annually. AML characterized by unbridled proliferation of progenitor cells block normal differentiation. Unfortunately, despite recent advances treatment, prognosis poor for almost all older adults half under age 60. Thus, novel effective therapies are urgently needed. Leukemic (LSCs) represent subset leukemic population contributing to relapse relatively refractory conventional treatments. Studies have shown that Salinomycin selectively kills cells. activated iron-mediated death (FERROPTOSIS) leads production reactive oxygen species (ROS). To reduce toxicity as well achieve slow sustained delivery Salinomycin, we generated biodegradable QUATRAMERTM polymeric nanoparticles (HSB-1216) (Hillstream Biopharma Inc.) permits intracellular this agent. Treatment human line MOLM-14 with HSB-1216 was associated significant (IC50 0.5 uM). Diverse lines including FLT-ITD-positive AML; p53-mutant positive NRAS-mutant [Mv4-11; HL-60; Kasumi, SKNO-1, KG-1, MOLM-13, NB4, THP-1, OCI-AML-3] were similarly sensitive between 0.25 2.0 uM; ROS-dependent killing). Colony assays these demonstrated significantly decreases clonogenic survival potently both Venetoclax-resistant FLT-3-inhibitorresistant lines. Moreover, combination decitabine synergistically inhibits growth The data support efficacy an anti-leukemic at non-hemotoxic concentrations. Taken together, results demonstrate method potent inhibitor highlight its potential treatment R/R AML. Conflict interest: Ownership: Equity ownership Hillstream Inc Advisory Board: SAB member