FSEN1

FSEN1 is an inhibitor of ferroptosis suppressor protein 1 (FSP1; IC₅₀ = 313 nM).¹ It is selective for FSP1 over NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1; IC₅₀ = >100 µM). FSEN1 induces cell death in GPX4^-/- H460 non-small cell lung cancer (NSCLC) cells (EC₅₀ = 69.36 nM) but not control H460 cells expressing Cas9 (H460Cas9). It sensitizes A549, Huh7, HCC1143, U2OS, SU-DHL-5, and T98G cancer cells to ferroptosis induced by (1S,3R)-RSL3 (Item No. 19288) when used at concentrations ranging from 10 to 1,000 nM. FSEN1 also sensitizes H460Cas9 cells, but not FSP1^-/- H460 cells, to cell death induced by the ferroptosis inhibitors dihydroartemisinin (Item No. 19846) or FINO₂ (Item No. 25096).

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1. Hendricks, J.M., Doubravsky, C., Wehri, E., et al. Identification of structurally diverse FSP1 inhibitors that sensitize cancer cells to ferroptosis. Cell Chem. Biol. 30(9), P1090-P1103 (2022).