{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:25:59Z","timestamp":1787498759850,"version":"build-2736575974"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T00:00:00Z","timestamp":1618963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre, Poland","award":["2018\/29\/N\/NZ7\/00432"],"award-info":[{"award-number":["2018\/29\/N\/NZ7\/00432"]}]},{"name":"Jagiellonian University Medical College, Krak\u00f3w, Poland","award":["N42\/DBS\/000133"],"award-info":[{"award-number":["N42\/DBS\/000133"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>This study aimed to assess the efficacy and explore the mechanisms of action of a potent phosphodiesterase (PDE)7A and a moderate PDE4B inhibitor GRMS-55 in a mouse model of autoimmune hepatitis (AIH). The concentrations of GRMS-55 and relevant biomarkers were measured in the serum of BALB\/c mice with concanavalin A (ConA)-induced hepatitis administered with GRMS-55 at two dose levels. A semi-mechanistic PK\/PD\/disease progression model describing the time courses of measured biomarkers was developed. The emetogenicity as a potential side effect of the studied compound was evaluated in the \u03b12-adrenoceptor agonist-induced anesthesia model. The results indicate that liver damage observed in mice challenged with ConA was mainly mediated by TNF-\u03b1 and IFN-\u03b3. GRMS-55 decreased the levels of pro-inflammatory mediators and the transaminase activities in the serum of mice with AIH. The anti-inflammatory properties of GRMS-55, resulting mainly from PDE7A inhibition, led to a high hepatoprotective activity in mice with AIH, which was mediated by an inhibition of pro-inflammatory signaling. GRMS-55 did not induce the emetic-like behavior. The developed PK\/PD\/disease progression model may be used in future studies to assess the potency and explore the mechanisms of action of new investigational compounds for the treatment of AIH.<\/jats:p>","DOI":"10.3390\/pharmaceutics13050597","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T21:25:10Z","timestamp":1619040310000},"page":"597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["PK\/PD Modeling of the PDE7 Inhibitor\u2014GRMS-55 in a Mouse Model of Autoimmune Hepatitis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-9709","authenticated-orcid":false,"given":"Artur","family":"\u015awierczek","sequence":"first","affiliation":[{"name":"Department of Pharmacokinetics and Physical Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Plutecka","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, 8 Skawi\u0144ska Street, 31-066 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marietta","family":"\u015alusarczyk","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gra\u017cyna","family":"Ch\u0142o\u0144-Rzepa","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u017cbieta","family":"Wyska","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Physical Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.3748\/wjg.v21.i1.60","article-title":"Autoimmune Hepatitis, One Disease with Many Faces: Etiopathogenetic, Clinico-Laboratory and Histological Characteristics","volume":"21","author":"Gatselis","year":"2015","journal-title":"World J. 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