{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE311nnn/GSE311556/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311556"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"BMX-001, a selective radioprotector in phase II clinical trials, can reverse radiation-induced fibrosis when given three weeks after radiation [RNA-seq]","description":"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.","dates":{"publication":"2026/07/01"},"accession":"GSE311556","cross_references":{"GSM":["GSM9326998","GSM9326987","GSM9326997","GSM9326989","GSM9326988","GSM9326999","GSM9326994","GSM9326993","GSM9326996","GSM9326995","GSM9326990","GSM9327001","GSM9327000","GSM9326992","GSM9326991","GSM9327002"],"GPL":["34328"],"GSE":["311556"],"taxon":["Mus musculus"],"PMID":["[42369229]"]}}