RSL3

RSL3 ((1S,3R)-RSL3) is an inhibitor of glutathione peroxidase 4 (GPX4) (ferroptosis activator), reduces the expression of GPX4 protein, and induces ferroptotic death of head and neck cancer cell. RSL3 increases the expression of p62 and Nrf2 and inactivates Keap1 in HN3-rslR cells^[1]. IC50 & Target:Glutathione peroxidase 4^[1] In Vitro:RSL3 (0-8 μM, 72 hours) potently reduces the viability of HN3 cells, with IC₅₀s of 0.48 μM in HN3 and 5.8 μM in HN3-rslR cells, respectively^[1].
RSL3 (0-8 μM, 24 hours) reduces the expression of GPX4 protein, increases the expression of p62 and Nrf2 and inactivates Keap1 in HN3-rslR cells^[1].

Ferroptosis-sensitive Cell Lines

Ferroptosis-sensitive Cells	Test Conditions
MCF10A-RAS[2]	0-10 μM; 48 h
MDA-MB-468[3]	0.1-1 μM; 24 h
PC-3[3]	0.01-1 μM; 24 h
Huh-7[3]	0.01-1 μM; 24 h
Raji[3]	0.01-1 μM; 24 h
MEF[3]	0.1-100 nM; 24 h
HT-22 neuron[4]	200 nM; 16 h
NCI-H508[5]	0.1-10 μM; 48 h
LoVo[5]	0.1-10 μM; 48 h
LS513[5]	0.1-10 μM; 48 h
SW480[5]	0.1-10 μM; 48 h
SW620[5]	0.1-10 μM; 48 h
SW1116[5]	0.1-10 μM; 48 h
DLD-1[5]	0.1-10 μM; 48 h
Caco-2[5]	0.1-10 μM; 48 h
HT-1080[6]	0-10 μM; 48 h; IC50 1.55 μM
MDA-MB-436[7]	0.1-2 μM; 24 h
HT-29[7]	0.1-2 μM; 24 h
U-373[7]	0.1-2 μM; 24 h
A549[8]	1 nM-100 μM; 24 h; IC50 0.5 μM
H1975[8]	1 nM-100 μM; 24 h; IC50 150 nM
MAD-MB-231[9]	0-10 μM; 96 h; IC50 0.71 μM
HCC1937[9]	0-10 μM; 96 h; IC50 0.85 μM

Ferroptosis-insensitive Cell Lines

Ferroptosis-insensitive Cells	Test Conditions
HS578T[10]	0-2.5 μM; 24 h
MCF10A[10]	0-2.5 μM; 24 h

In Vivo:RSL3 (100 mg/kg, Intratumorally twice per week for 20 days) significantly inhibits the growth of tumor in combination with Trigonelline (HY-N0414) in mice bearing HN3R cells^[1].