a, The protein level of DHCR7 in SC5D KO HEK293T cells expressing sgRNAs targeting DHCR7 detected by Immunoblotting. b, g, The concentration of 7-DHC in WT and DHCR7 KO HEK293T cells after treatment of indicated concentrations of AY9944 (b) or cariprazine (g) for 48 h. c, h, Cell viability of WT, DHCR7 KO and SC5D KO HEK293T cells treated with RSL3 for 8 h after pretreatment of AY9944 (100 nM) (c) or cariprazine (100 nM) (h) for 48 h. d, Schema of cholesterol biosynthesis pathway. e, i, Cell viability of U937 and SNU-1 cells treated with RSL3 for 18 h after pretreatment of AY9944 (100 nM) (e) or cariprazine (100 nM) (i) for 48 h. f, j, Representative autoxidation inhibited by indicated concentration of AY9944 (f) and cariprazine (j). k, Levels of 7-DHC in HEK293T cells after treatment of indicated dose of ethanol-dissolved 7-DHC or MβCD-coated 7-DHC for 24 h. l, Cell viability of HEK293T cells treated with RSL3 for 8 h after pretreatment of ethanol-dissolved 7-DHC(25 μM) or MβCD-coated 7-DHC (25 μM) for 24 h. m, Cell viability of HEK293T cells treated with RSL3 for 8 h after pretreatment of MβCD-coated sterols (25 μM) for 24 h. Data are representative of at least two (a-c and e-m) independent experiments. Data are mean ± s.d. of n=3 biological replicates (b, c, e, g-I and k-m). Statistical analysis was performed using two-way ANOVA (b, g and k); *P < 0.05, ****P < 0.0001, ns, not significant.