In vitro and in vivo pharmacokinetic characterization of LMT-28 as a novel small molecular interleukin-6 inhibitor
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Ahn, Sung-Hoon | - |
dc.contributor.author | Heo, Tae-Hwe | - |
dc.contributor.author | Jun, Hyun-Sik | - |
dc.contributor.author | Choi, Yongseok | - |
dc.date.accessioned | 2021-08-31T04:38:48Z | - |
dc.date.available | 2021-08-31T04:38:48Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2020-04 | - |
dc.identifier.issn | 1011-2367 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/56706 | - |
dc.description.abstract | Objective: Interleukin-6 (IL-6) is a T cell-derived B cell stimulating factor which plays an important role in inflammatory diseases. In this study, the pharmacokinetic properties of LMT-28 including physicochemical property, in vitro liver microsomal stability and an in vivo pharmacokinetic study using BALB/c mice were characterized. Methods: LMT-28 has been synthesized and is being developed as a novel therapeutic IL-6 inhibitor. The physicochemical properties and in vitro pharmacokinetic profiles such as liver microsomal stability and Madin-Darby canine kidney (MDCK) cell permeability assay were examined. For in vivo pharmacokinetic studies, pharmacokinetic parameters using BALB/c mice were calculated. Results: The logarithm of the partition coefficient value (LogP; 3.65) and the apparent permeability coefficient values (P-app; 9.7x10(-6) cm/s) showed that LMT-28 possesses a moderatehigh cell permeability property across MDCK cell monolayers. The plasma protein binding rate of LMT-28 was 92.4% and mostly bound to serum albumin. The metabolic half-life (t(1/2)) values of LMT-28 were 15.3 min for rat and 21.9 min for human at the concentration 1 mu M. The area under the plasma drug concentration-time curve and C-max after oral administration (5 mg/kg) of LMT-28 were 302 +/- 209 h.ng/mL and 137 +/- 100 ng/mL, respectively. Conclusion: These data suggest that LMT-28 may have good physicochemical and pharmacokinetic properties and may be a novel oral drug candidate as the first synthetic IL-6 inhibitor to ameliorate mammalian inflammation. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | ASIAN-AUSTRALASIAN ASSOC ANIMAL PRODUCTION SOC | - |
dc.subject | SHAKE-FLASK METHOD | - |
dc.subject | SOLUBILITY | - |
dc.subject | BLOCKADE | - |
dc.subject | IL-6 | - |
dc.title | In vitro and in vivo pharmacokinetic characterization of LMT-28 as a novel small molecular interleukin-6 inhibitor | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Jun, Hyun-Sik | - |
dc.contributor.affiliatedAuthor | Choi, Yongseok | - |
dc.identifier.doi | 10.5713/ajas.19.0463 | - |
dc.identifier.scopusid | 2-s2.0-85082188120 | - |
dc.identifier.wosid | 000516627500017 | - |
dc.identifier.bibliographicCitation | ASIAN-AUSTRALASIAN JOURNAL OF ANIMAL SCIENCES, v.33, no.4, pp.670 - 677 | - |
dc.relation.isPartOf | ASIAN-AUSTRALASIAN JOURNAL OF ANIMAL SCIENCES | - |
dc.citation.title | ASIAN-AUSTRALASIAN JOURNAL OF ANIMAL SCIENCES | - |
dc.citation.volume | 33 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 670 | - |
dc.citation.endPage | 677 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.identifier.kciid | ART002568932 | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
dc.relation.journalResearchArea | Agriculture | - |
dc.relation.journalWebOfScienceCategory | Agriculture, Dairy & Animal Science | - |
dc.subject.keywordPlus | SHAKE-FLASK METHOD | - |
dc.subject.keywordPlus | SOLUBILITY | - |
dc.subject.keywordPlus | BLOCKADE | - |
dc.subject.keywordPlus | IL-6 | - |
dc.subject.keywordAuthor | Interleukin-6 | - |
dc.subject.keywordAuthor | gp130 | - |
dc.subject.keywordAuthor | Pharmacokinetics | - |
dc.subject.keywordAuthor | Metabolic stability | - |
dc.subject.keywordAuthor | Inflammation | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(02841) 서울특별시 성북구 안암로 14502-3290-1114
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.