{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:25:58Z","timestamp":1790126758184,"version":"4.0.1"},"reference-count":26,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK37175"],"award-info":[{"award-number":["R01 DK37175"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["P30-DK079638"],"award-info":[{"award-number":["P30-DK079638"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["1-11-BS-194"],"award-info":[{"award-number":["1-11-BS-194"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL147108"],"award-info":[{"award-number":["R01 HL147108"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:p> Loss of muscle proteins increases the morbidity and mortality of patients with chronic kidney disease (CKD), and there are no reliable preventive treatments. We uncovered a STAT3\/CCAAT-enhancer-binding protein-\u03b4 to myostatin signaling pathway that activates muscle protein degradation in mice with CKD or cancer; we also identified a small-molecule inhibitor of STAT3 (TTI-101) that blocks this pathway. To evaluate TTI-101 as a treatment for CKD-induced cachexia, we measured TTI-101 pharmacokinetics and pharmacodynamics in control and CKD rats that were orally administered TTI-101or its diluent. The following two groups of gavage-fed rats were studied: sham-operated control rats and CKD rats. Plasma was collected serially (0, 0.25, 0.5, 1, 2, 4, 8, and 24 h) following TTI-101 administration (at oral doses of 0, 10, 30, or 100 mg\/kg). Plasma levels of TTI-101 were measured by LC-MS\/MS, and pharmacokinetic results were analyzed with the PKSolver program. Plasma TTI-101 levels increased linearly with doses; the maximum plasma concentrations and time to maximal plasma levels (~1 h) were similar in sham-operated control rats and CKD rats. Notably, gavage treatment of TTI-101 for 3 days produced TTI-101 muscle levels in sham control rats and CKD rats that were not significantly different. CKD rats that received TTI-101 for 7 days had suppression of activated STAT3 and improved muscle grip strength; there also was a trend for increasing body and muscle weights. TTI-101 was tolerated at doses of 100 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup> for 7 days. These results with TTI-101 in rats warrant its development as a treatment for cachexia in humans. <\/jats:p>","DOI":"10.1152\/ajprenal.00603.2019","type":"journal-article","created":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T08:13:40Z","timestamp":1590999220000},"page":"F84-F92","source":"Crossref","is-referenced-by-count":24,"title":["Pharmacokinetics and pharmacodynamics of TTI-101, a STAT3 inhibitor that blocks muscle proteolysis in rats with chronic kidney disease"],"prefix":"10.1152","volume":"319","author":[{"given":"Liping","family":"Zhang","sequence":"first","affiliation":[{"name":"Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlan","family":"Dong","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihong","family":"Chen","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas K.","family":"Eckols","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, Department of Infectious Disease, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moses M.","family":"Kasembeli","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, Department of Infectious Disease, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Tweardy","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, Department of Infectious Disease, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas"},{"name":"Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Mitch","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004100842"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-008-0574-6"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8368"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00039.2012"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022538"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2003.10.001"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2015.200"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18330"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/2159739"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e3181856241"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-1468"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112344"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-280123"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.hjc.2015.11.001"},{"key":"B15","first-page":"A57","volume":"3","author":"Schoolwerth AC","year":"2006","journal-title":"Prev Chronic Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.641514"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx431"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2014.112"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2010.28608B"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004783"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008060628"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.07.012"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-176917"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.090275"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009060571"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2010.01.007"}],"updated-by":[{"DOI":"10.1152\/ajprenal.00603.2019_cor","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T00:00:00Z","timestamp":1641340800000}}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00603.2019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T13:26:23Z","timestamp":1594041983000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajprenal.00603.2019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,1]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,7,1]]}},"alternative-id":["10.1152\/ajprenal.00603.2019"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00603.2019","relation":{"correction":[{"id-type":"doi","id":"10.1152\/ajprenal.00603.2019_COR","asserted-by":"object"}]},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,1]]}}}