KR33426, [2-(2,5-dichlorophenyl)-5-methyloxazol-4yl]carbonylguanidine, is a novel compound to be effective on mouse systemic lupus erythematosus
- Authors
- Lee, Geun-Hee; Oh, Jin-Mi; Kim, Hyun-Sun; Yoon, Won-Kee; Yi, Kyu Yang; Yang, Young; Han, Seung-Hyun; Lee, Sunkyung; Moon, Eun-Yi
- Issue Date
- Oct-2011
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- BAFF; KR33426; Carbonylguanidine derivative; B cell; Systemic lupus erythematosus
- Citation
- EUROPEAN JOURNAL OF PHARMACOLOGY, v.668, no.3, pp 459 - 466
- Pages
- 8
- Journal Title
- EUROPEAN JOURNAL OF PHARMACOLOGY
- Volume
- 668
- Number
- 3
- Start Page
- 459
- End Page
- 466
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/12472
- DOI
- 10.1016/j.ejphar.2011.07.026
- ISSN
- 0014-2999
1879-0712
- Abstract
- B cell-activating factor (BAFF) is a key regulator of B lymphocyte development. Signals from BAFF are transmitted through binding to a specific BAFF receptor (BAFF-R). Here, we established screening method to find a specific inhibitor for the interference of BAFF-BAFF-R interactions. We screened oxazole-4-carbonylguanidine derivatives and selected KR33426, [2-(2,5-dichlorophenyl)-5-methyloxazol-4yl]carbonylguanidine, as a candidate to interfere BAFF-BAFF-R interactions. KR33426 inhibited BAFF-mediated anti-apoptotic effect on splenocytes as judged by hypodiploid cell formation. KR33426 also increased the degradation of procaspase-3 that was inhibited by BAFF protein. In addition, we examined whether KR33426 was effective on the treatment of systemic lupus erythematosus-like symptom in MRLlpr/lpr mouse. When 5 or 10 mg/kg KR33426 was intraperitoneally administered to MRLlpr/lpr mice for 4 weeks, histopathological changes were ameliorated in the narrowed space between renal glomerulus and glomerulus capsule. KR33426 reduced B220(+) B cell population and B cell mitogen, lipopolysaccharide-stimulated lymphocyte proliferation in splenocytes. KR33426 attenuated an increase in CD43(-)IgM(+) immature pro-B and a decrease in CD21(+) IgM(+) T2-B and IgD(+) IgM(-)recirculating-B cells on B cell development. Data show that KR33426 inhibits BAFF-BAFF-R interactions and it is effective on the treatment of systemic lupus erythematosus-like symptom in MRLlpr/lpr mice. Thus, it suggests that KR33426 is a novel candidate to develop anti-autoimmune therapeutics by the interference of BAFF-BAFF-R interactions, specifically. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.
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