{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T04:10:11Z","timestamp":1730434211694,"version":"3.28.0"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2002,4,1]],"date-time":"2002-04-01T00:00:00Z","timestamp":1017619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The reactivity of the thiol moiety of the active main metabolite (M-I) of esonarimod (kE-298), a novel anti-rheumatic agent, was investigated in rats. After repeated oral administration of 14C-kE-298, the radioactivity decreased rapidly and no tendency towards accumulation was found, in marked contrast to other common SH-group-containing drugs. At 30 min after intravenous administration of 14C-M-I to rats, the concentration of the 14C-M-I plasma protein conjugate in plasma was extremely low at 0.143 nmol mL\u22121 (0.66% of total plasma radioactivity). The 14C-M-I plasma protein conjugate that formed in rat plasma was mixed disulfide with plasma protein. After intravenous administration of synthetic 14C-M-I plasma protein conjugate to rats, the radioactivity in plasma decreased rapidly, with the terminal half-life at 6.90 h. In-vitro, the 14C-M-I plasma protein conjugate was readily dissociated by the endogenous thiol compounds, cysteine and glutathione. These results suggest that the reactivity of the thiol moiety of M-I is extremely low. Furthermore, the 14C-M-I plasma protein conjugate decreased rapidly in-vivo, which would be related to interaction with endogenous thiol compounds. These properties of M-I are principally responsible for the zero accumulation in rat tissues. kE-298 could therefore be expected to have reduced adverse effects compared with other SH-group-containing anti-rheumatic drugs.<\/jats:p>","DOI":"10.1211\/0022357021778763","type":"journal-article","created":{"date-parts":[[2002,10,11]],"date-time":"2002-10-11T20:14:04Z","timestamp":1034367244000},"page":"493-498","source":"Crossref","is-referenced-by-count":0,"title":["Formation of a disulfide protein conjugate of the SH-group-containing metabolite (M-I) of esonarimod (kE-298) and its elimination in rats"],"prefix":"10.1093","volume":"54","author":[{"given":"Masatoshi","family":"Hasegawa","sequence":"first","affiliation":[{"name":"Drug Metabolism and Toxicology Research Center, Taisho Pharmaceutical Co., Ltd , 1\u2013403 Yoshino-Cho, Saitama-Shi, Saitama 330\u20138530,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoko","family":"Omi","sequence":"additional","affiliation":[{"name":"Drug Metabolism and Toxicology Research Center, Taisho Pharmaceutical Co., Ltd , 1\u2013403 Yoshino-Cho, Saitama-Shi, Saitama 330\u20138530,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromi","family":"Endo","sequence":"additional","affiliation":[{"name":"Drug Metabolism and Toxicology Research Center, Taisho Pharmaceutical Co., Ltd , 1\u2013403 Yoshino-Cho, Saitama-Shi, Saitama 330\u20138530,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideo","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Drug Metabolism and Toxicology Research Center, Taisho Pharmaceutical Co., Ltd , 1\u2013403 Yoshino-Cho, Saitama-Shi, Saitama 330\u20138530,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shohei","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Drug Metabolism and Toxicology Research Center, Taisho Pharmaceutical Co., Ltd , 1\u2013403 Yoshino-Cho, Saitama-Shi, Saitama 330\u20138530,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2002,4,1]]},"reference":[{"key":"2024103109380024700_cit1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1254\/fpj.76.117","article-title":"Pharmacological studies of new sulfydryl compounds 2-mercapto 2-methyl-propanoyl-L-cysteine (SA96). 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