{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T13:05:00Z","timestamp":1763643900715,"version":"3.40.5"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015570","name":"Blood Cancer UK","doi-asserted-by":"crossref","award":["13005"],"award-info":[{"award-number":["13005"]}],"id":[{"id":"10.13039\/501100015570","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100015570","name":"Blood Cancer UK","doi-asserted-by":"crossref","award":["19007"],"award-info":[{"award-number":["19007"]}],"id":[{"id":"10.13039\/501100015570","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C5759\/A20971"],"award-info":[{"award-number":["C5759\/A20971"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"cancer research uk","doi-asserted-by":"crossref","award":["C5759\/A27412"],"award-info":[{"award-number":["C5759\/A27412"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C7932\/A25142"],"award-info":[{"award-number":["C7932\/A25142"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Leukemia UK","award":["2019\/JGF\/003"],"award-info":[{"award-number":["2019\/JGF\/003"]}]},{"name":"CRUK Scotland Centre funding","award":["CTRQQR-2021\\100006"],"award-info":[{"award-number":["CTRQQR-2021\\100006"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Myelofibrosis is a myeloproliferative neoplasm (MPN) which typically results in reduced length and quality of life due to systemic symptoms and blood count changes arising from fibrotic changes in the bone marrow. While the JAK2 inhibitor ruxolitinib provides some clinical benefit, there remains a substantial unmet need for novel targeted therapies to better modify the disease process or eradicate the cells at the heart of myelofibrosis pathology. Repurposing drugs bypasses many of the hurdles present in drug development, such as toxicity and pharmacodynamic profiling. To this end we undertook a re-analysis of our pre-existing proteomic data sets to identify perturbed biochemical pathways and their associated drugs\/inhibitors to potentially target the cells driving myelofibrosis. This approach identified CBL0137 as a candidate for targeting <jats:italic>Jak2<\/jats:italic> mutation-driven malignancies. CBL0137 is a drug derived from curaxin targeting the Facilitates Chromatin Transcription (FACT) complex. It is reported to trap the FACT complex on chromatin thereby activating p53 and inhibiting NF-kB activity. We therefore assessed the activity of CBL0137 in primary patient samples and murine models of <jats:italic>Jak2<\/jats:italic>-mutated MPN and found it preferentially targets CD34+ stem and progenitor cells from myelofibrosis patients by comparison with healthy control cells. Further we investigate its mechanism of action in primary haemopoietic progenitor cells and demonstrate its ability to reduce splenomegaly and reticulocyte number in a transgenic murine model of myeloproliferative neoplasms.<\/jats:p>","DOI":"10.1371\/journal.pone.0286412","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T17:34:51Z","timestamp":1685468091000},"page":"e0286412","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of curaxin as a potential new therapeutic for JAK2 V617F mutant patients"],"prefix":"10.1371","volume":"18","author":[{"given":"Stella","family":"Pearson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rognvald","family":"Blance","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Ching","family":"Hsieh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bethany","family":"Geary","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio M. 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