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. Author manuscript; available in PMC: 2023 Jul 18.
Published in final edited form as: Sci Transl Med. 2023 Jan 18;15(679):eabq6288. doi: 10.1126/scitranslmed.abq6288

Figure 2: Treatment with YTX-7739 promotes a terminal UPR response and sensitizes to TMZ and radiation.

Figure 2:

(A) Relative mRNA expression as compared to DMSO (control) and (B) immunoblot analysis of ER stress markers in 83 treated with YTX-7739 for 48h. (C) Cell viability of 83 treated with YTX-7739 in combination with inhibitors of ER stress (PBA: 4mM; Azoramide: 50μM; Salubrinal: 25μM), IRE1 (4μ8C: 25μM; NSC95682: 20μM) and JNK (SP600125: 20μM) for 96h. (D) Overview of de novo lipid synthesis (DNLS) pathway. (E) Cell viability of 83 treated with YTX-7739 (0.5μM) in combination with inhibitors of FASN (GSK2194069: 25–50nM) or ACC (CP-640186: 2.5–5μM) for 96h. (F) Fold-change in HDR/NHEJ normalized to cell viability in 83 treated with YTX-7739. (G-I) MGG6 were pretreated with YTX-7739 followed by TMZ or RT. (G) Immunoblot analysis of DNA repair and damage at 72h after treatment with YTX-7739 and TMZ (5μM). (H-I) Secondary sphere count 9 days after co-treatment with TMZ (H) or RT (I). (J-M) M120 were pretreated with YTX-7739, followed by TMZ or RT. (J) Immunoblot analysis after treatment with YTX-7739 and TMZ (100μM). (K) Representative micrographs of neurospheres. Scale bar, 100μm. (L-M) Secondary sphere count after co-treatment with TMZ (H) or RT (I). ****P<0.0001; *** P<0.001; **P<0.01; *P<0.05