GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE311nnn/GSE311556/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311556GEOGSEfalseBMX-001, a selective radioprotector in phase II clinical trials, can reverse radiation-induced fibrosis when given three weeks after radiation [RNA-seq]Colorectal cancer is a common yet survivable malignancy, partly due to the addition of chemoradiation to treatment regimens. Many patients suffer treatment-related side effects such as pain, diarrhea, and myelosuppression, and increasing toleration of treatment has the potential to improve outcomes. BMX-001, a superoxide dismutase mimetic, is currently in clinical trials as a selective radioprotector for anal and rectal cancer; however, the mechanism by which BMX-001 exerts selective radioprotection of healthy tissue over cancer tissue, particularly when administered at physiologically achievable doses, is not well understood. BMX-001 was given before and during chemoradiation and did not interfere with chemoradiation-induced cancer cell killing in mouse models. In vitro, BMX-001 still induced cancer cell killing in the presence of exogenous catalase, suggesting that BMX-001’s anti-tumor activity is not solely reliant on hydrogen peroxide production. BMX-001 exerted robust acute radioprotection in radiation mouse models five and nine days post-radiation. To assess whether BMX-001’s protection is contingent on Nrf2 expression, we evaluated the effect of BMX-001 on 5-FU treated bone marrow, where Nrf2 is crucial to maintaining hematopoietic stem cell niches. Interestingly, BMX-001 could still exert some chemoprotection in mice without functional Nrf2. To assess whether BMX-001 had any functional effects on protein oxidation status, we performed mass spectrometry on sulfenylated proteins in bone marrow treated with 5-FU in wildtype mice and mice without Nrf2. We found that BMX-001 given before 5-FU treatment resulted in the sulfenylation of CRTC2 and CBP, two proteins involved in CREB signaling and known to enhance Nrf2 activity. We also found that BMX-001 with 5-FU treatment enhanced DPYD sulfenylation, a protein known to detoxify 5-FU, and ALDH7A1 sulfenylation, a protein known to detoxify aldehydes. Together, these results suggest that BMX-001 can protect against oxidative stress in normal tissue via Nrf2 dependent and independent mechanisms.2026/07/01GSE311556GSM9326998GSM9326987GSM9326997GSM9326989GSM9326988GSM9326999GSM9326994GSM9326993GSM9326996GSM9326995GSM9326990GSM9327001GSM9327000GSM9326992GSM9326991GSM932700234328311556Mus musculus[42369229]