{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T21:18:27Z","timestamp":1785705507538,"version":"3.56.0"},"reference-count":24,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T00:00:00Z","timestamp":1665360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"publisher","award":["R01FD006106"],"award-info":[{"award-number":["R01FD006106"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Preclinical studies show seliciclib (R-roscovitine) suppresses neoplastic corticotroph proliferation and pituitary adrenocorticotrophic hormone (ACTH) production.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate seliciclib as an effective pituitary-targeting treatment for patients with Cushing disease (CD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two prospective, open-label, phase 2 trials, conducted at a tertiary referral pituitary center, included adult patients with de novo, persistent, or recurrent CD who received oral seliciclib 400 mg twice daily for 4 consecutive days each week for 4 weeks. The primary endpoint in the proof-of-concept single-center study was normalization of 24-hour urinary free cortisol (UFC; \u2264 50 \u00b5g\/24 hours) at study end; in the pilot multicenter study, primary endpoint was UFC normalization or \u2265 50% reduction in UFC from baseline to study end.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sixteen patients were consented and 9 were treated. Mean UFC decreased by 42%, from 226.4 \u00b1 140.3 \u00b5g\/24 hours at baseline to 131.3 \u00b1 114.3 \u00b5g\/24 hours by study end. Longitudinal model showed significant UFC reductions from baseline to each treatment week. Three patients achieved \u2265 50% UFC reduction (range, 55%-75%), and 2 patients exhibited 48% reduction; none achieved UFC normalization. Plasma ACTH decreased by 19% (P = 0.01) in patients who achieved \u2265 48% UFC reduction. Three patients developed grade \u2264 2 elevated liver enzymes, anemia, and\/or elevated creatinine, which resolved with dose interruption\/reduction. Two patients developed grade 4 liver-related serious adverse events that resolved within 4 weeks of seliciclib discontinuation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Seliciclib may directly target pituitary corticotrophs in CD and reverse hypercortisolism. Potential liver toxicity of seliciclib resolves with treatment withdrawal. The lowest effective dose requires further determination.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgac588","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T16:22:09Z","timestamp":1665418929000},"page":"726-735","source":"Crossref","is-referenced-by-count":27,"title":["Treatment of Cushing Disease With Pituitary-Targeting Seliciclib"],"prefix":"10.1210","volume":"108","author":[{"given":"Ning-Ai","family":"Liu","sequence":"first","affiliation":[{"name":"Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center , Los Angeles, CA 90048 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anat","family":"Ben-Shlomo","sequence":"additional","affiliation":[{"name":"Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center , Los Angeles, CA 90048 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John 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