RSL3 是一种不依赖 VDAC 的铁死亡激活剂，对携带致癌 Ras 的肿瘤细胞具有选择性。 它是谷胱甘肽过氧化物酶 4 的抑制剂，可抑制阻断 GSH 合成的半胱氨酸/谷氨酸氨基酸转运系统 xc-，IC50为100 nM。

RSL3 is a VDAC-independent ferroptosis activator with selectivity for tumor cells bearing oncogenic RAS. RSL3 is the inhibitor of the glutathione peroxidase 4, which can inhibit the cysteine/glutamate amino acid transporter system xc- that blocks GSH synthesis (IC50: 100 nM).

Ferroptosis-inducing compounds inactivate GPX4 by direct binding or by depleting glutathione.After binding to GPX4, RSL3 inactivates GPX4 to induce ROS production from lipid peroxidation. RSL3's ability to induce synthetic lethality with oncogenic RAS is rapid and quite potent. This compound inhibits the growth of BJ-TERT/LT/ST/RASV12 and DRD cells as low as 10 ng/mland started to kill sensitive cells as early as 8 hr after treatment[1][2].

Prostaglandin-endoperoxide synthase (PTGS) is the key enzyme in prostaglandin biosynthesis. There are two isozymes of PTGS: a constitutive PTGS1 and an inducible PTGS2. PTGS2 encoding cyclooxygenase-2 (COX-2) is significantly upregulated after treatment with RSL3 and erastin in mice[1].

TERT/LT/ST/RASV12 cells are seeded in 10 cm dishes and treated with 1 µM staurosporine, 10 µg/ml erastin, 20 µg/ml RSL5, and 1 µg/ml RSL3 for 16 hr. Both dying cells and live cells in each 10 cm dish are harvested and collected in the same 15 ml tubes by centrifuging cell suspension at 1000 rpm for 5 min. (Only for Reference)

1219810-16-8

C23H21ClN2O5

440.88

RSL3 1S;1S,3R-RSL3

DMSO:44.1 mg/mL (100 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years