{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:15:38Z","timestamp":1790964938645,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T00:00:00Z","timestamp":1735344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korean government","award":["RS-2024-00399681"],"award-info":[{"award-number":["RS-2024-00399681"]}]},{"name":"Korean government","award":["RS-2024-00339289"],"award-info":[{"award-number":["RS-2024-00339289"]}]},{"name":"Korean government","award":["RS-2024-00442484"],"award-info":[{"award-number":["RS-2024-00442484"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>NF2-related schwannomatosis (NF2-SWN) is associated with multiple benign tumors in the nervous system. NF2-SWN, caused by mutations in the NF2 gene, has developed into intracranial and spinal schwannomas. Because of the high surgical risk and frequent recurrence of multiple tumors, targeted therapy is necessary. However, there are no approved drugs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We examined the action mechanism of PRG-N-01, a candidate molecule for NF2-SWN, through the direct binding assay and mass spectrometry. For in vitro anti-proliferative experiments, primary cells derived from the NF2 mouse model and patient tumors were treated with PRG-N-01. The in vivo therapeutic and preventive efficacy was validated via intraperitoneal and oral administration in the NF2 mouse model (Postn-Cre; Nf2f\/f). Gene expression profile in the DRG of the mouse model was explored by RNA sequencing. The pharmacological properties of PRG-N-01 were analyzed through the preclinical study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>PRG-N-01 binds to the N-terminal extremity of TGF\u03b2R1 (T\u03b2R1) kinase domain, where T\u03b2R1 and RKIP interact, inhibiting the binding and preventing degradation of RKIP. In vivo administration in the mouse model suppressed schwannoma progression in the DRG. Early oral administration of the PRG-N-01 also demonstrated preventive effects on NF2-SWN. PRG-N-01 treatment suppressed tumor growth genes while upregulating genes related to for normal cell metabolism and Schwann cell differentiation in DRG. PRG-N-01 showed druggable properties through the preclinical study, including ADME, pharmacodynamics, pharmacokinetics, and toxicology.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Together, our study provides the rationale and critical data for a prospective clinical trial of PRG-N-01 in NF2-SWN patients indicating PRG-N-01 as a promising candidate for the treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noae282","type":"journal-article","created":{"date-parts":[[2024,12,28]],"date-time":"2024-12-28T06:32:26Z","timestamp":1735367546000},"page":"1241-1255","source":"Crossref","is-referenced-by-count":4,"title":["Therapeutic effect of novel drug candidate, PRG-N-01, on NF2 syndrome-related tumor"],"prefix":"10.1093","volume":"27","author":[{"given":"Yeon-Ho","family":"Chung","sequence":"first","affiliation":[{"name":"Rare Disease R&D Center, PRG S&T Co., Ltd , Busan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soyoung","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, College of Natural Science, Pusan National University , Busan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moonyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Korea University College of Medicine , Seoul,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongwon","family":"Lee","sequence":"additional","affiliation":[{"name":"Brain Korea 21 Plus Project for Biomedical Science, Korea University College of Medicine , Seoul,","place":["Republic of Korea"]},{"name":"Department of Biomedical Sciences, Korea University College of Medicine , Seoul,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeongseon","family":"Ji","sequence":"additional","affiliation":[{"name":"Rare Disease R&D Center, PRG S&T Co., Ltd , Busan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Jin","family":"Song","sequence":"additional","affiliation":[{"name":"Rare Disease R&D Center, PRG S&T Co., Ltd , Busan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Gyun","family":"Woo","sequence":"additional","affiliation":[{"name":"Rare Disease R&D Center, PRG S&T Co., Ltd , Busan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunbyeol","family":"Shin","sequence":"additional","affiliation":[{"name":"Rare Disease R&D Center, PRG S&T Co., Ltd , Busan,","place":["Republic of 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Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Han","sequence":"additional","affiliation":[{"name":"Rare Disease R&D Center, PRG S&T Co., Ltd , Busan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Rae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Korea University College of Medicine , Seoul,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungmin","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Korea University College of Medicine , Seoul,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bae-Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Rare Disease R&D Center, PRG S&T Co., Ltd , Busan ,","place":["countryRepublic of 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