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Two features set the pace observed in trials: Long half-life
Yu DX, Di Giorgio FP, Yao J, Marchetto MC, Brennand K, Wright R, et al
In this protective role, ATF4 drives the expression of the chaperone heat shock protein family A (Hsp70) member 5 (HSPA5), which in turn stabilizes and enhances the activity of GPX4, thereby inhibiting ferroptotic cell death ( In ferroptosis resistant melanoma cells, CHAC1 was shown to be upregulated by NRF2 independent from ER stress signaling alongside the Aldo-Keto Reductase Family 1 Member C1 (AKR1C1) capable of degrading lipid radicals ( CHAC1 , most melanoma cell lines appear to be resistant against ferroptosis
