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LPS-induced endotoxemia, concanavalin A (ConA)-induced hepatitis, and collagen-induced arthritis (CIA) animal models were used for\n                      <jats:italic>in vivo<\/jats:italic>\n                      evaluation. The potency of the investigated compounds was evaluated using PK\/PD and PK\/PD\/disease progression modeling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      GRMS-55 is a potent hrPDE7A and hrPDE1B inhibitor, while (\u00b1)-LSF most strongly inhibits hrPDE3A and hrPDE4B. GRMS-55 decreased TNF-alpha levels\n                      <jats:italic>in vivo<\/jats:italic>\n                      and CIA progression with\n                      <jats:italic>IC<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>50<\/jats:italic>\n                      <\/jats:sub>\n                      of 1.06 and 0.26\u00a0mg\/L, while (\u00b1)-LSF with\n                      <jats:italic>IC<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>50<\/jats:italic>\n                      <\/jats:sub>\n                      of 5.80 and 1.06\u00a0mg\/L, respectively. Moreover, GRMS-55 significantly ameliorated symptoms of ConA-induced hepatitis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PDE4B but not PDE4D inhibition appears to be mainly engaged in anti-inflammatory activity of the studied compounds. GRMS-55 and (\u00b1)-LSF seem to be promising candidates for future studies on the treatment of immune-related diseases. The developed PK\/PD models may be used to assess the anti-inflammatory and anti-arthritic potency of new compounds for the treatment of rheumatoid arthritis and other inflammatory disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11095-019-2727-z","type":"journal-article","created":{"date-parts":[[2020,1,2]],"date-time":"2020-01-02T14:04:30Z","timestamp":1577973870000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Comparative Assessment of the New PDE7 Inhibitor \u2013 GRMS-55 and Lisofylline in Animal Models of Immune-Related Disorders: A PK\/PD Modeling Approach"],"prefix":"10.1007","volume":"37","author":[{"given":"Artur","family":"\u015awierczek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krzysztof","family":"Pociecha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marietta","family":"\u015alusarczyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gra\u017cyna","family":"Ch\u0142o\u0144-Rzepa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Ba\u015b","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacek","family":"Mlynarski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krzysztof","family":"Wi\u0119ckowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Zadro\u017cna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Nowak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4798-0574","authenticated-orcid":false,"given":"El\u017cbieta","family":"Wyska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,1,2]]},"reference":[{"key":"2727_CR1","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1038\/sj.bjp.0702911","volume":"128","author":"CD Manning","year":"1999","unstructured":"Manning CD, Burman M, Christensen SB, Cieslinski LB, Essayan DM, Grous M, Torphy TJ, Barnette MS. 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In addition, the descriptions of <i>V<\/i><sub><i>1(ROL)<\/i><\/sub> and <i>V<\/i><sub><i>1(GRMS-55)<\/i><\/sub> were imprecise and the reference number in the footnote below this table should be (9). The corrected Table appears below.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"19"}}