A 12-week Randomized, Double-blind, Placebo-controlled, Multicenter, Multiple Sequential Dose Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Apo805K1 in Subjects With Moderate to Severe Chronic Plaque Psoriasis

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of 12 weeks of treatment with Apo805K1 in subjects with moderate to severe chronic plaque psoriasis.

开始日期2011-11-01

申办/合作机构

ApoPharma, Inc.

100 项与 Orilotimod potassium 相关的临床结果

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100 项与 Orilotimod potassium 相关的转化医学

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100 项与 Orilotimod potassium 相关的专利（医药）

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项与 Orilotimod potassium 相关的文献（医药）

Journal of Inflammation Research

C/EBPβ Promotes LPS-Induced IL-1β Transcription and Secretion in Alveolar Macrophages via NOD2 Signaling

Article

作者: Zhang, Yibo ; Wen, Haiyun ; Zhang, Guixin ; Liu, Jin ; Lan, Bowen ; Dong, Xuanchi ; Ge, Peng ; Yang, Qi ; Luo, Yalan ; Chen, Hailong

ObjectiveC/EBPβ, a crucial transcription factor, regulates innate immunity and inflammatory responses. However, the role played by C/EBPβ in alveolar macrophage (AM) inflammatory responses remains unknown. This study aimed to investigate the role and mechanism of C/EBPβ in alveolar macrophages (AMs) from the transcriptional level and to search for natural compounds targeting C/EBPβ.MethodsRat AMs were infected with Lv-sh-C/EBPβ and treated with LPS, and the expression levels of iNOS, TNF-α, IL-6, and IL-1β were measured by RT-qPCR, Western blotting, and ELISA. Mechanistically, transcriptome sequencing (RNA-seq) revealed changes in gene expression patterns in AMs after LPS stimulation and C/EBPβ knockdown. Functional enrichment analyses and rescue experiments identified and validated inflammation-associated cell signaling pathways regulated by C/EBPβ. Furthermore, virtual screening was used to search for natural compounds that inhibit C/EBPβ with the structure of helenalin as a reference.ResultsFollowing stimulation with LPS, AMs exhibited an increased expression of C/EBPβ. C/EBPβ knockdown significantly decreased the expression levels of inflammatory mediators. A total of 374 differentially expressed genes (DEGs) were identified between LPS-stimulated C/EBPβ knockdown and negative control cells. The NOD-like receptor signaling may be a key target for C/EBPβ, according to functional enrichment analyses of the DEGs. Further experiments showed that the muramyl dipeptide (MDP, NOD2 agonist) reversed the downregulation of inflammatory mediators and the NF-κB pathway caused by the C/EBPβ knockdown. The virtual screening revealed that N-caffeoyltryptophan, orilotimod, and petasiphenone have comparable pharmacological properties to helenalin (a known C/EBPβ inhibitor) and demonstrate a great binding capacity to C/EBPβ.ConclusionAblation of C/EBPβ may attenuate LPS-induced inflammatory damage in AMs by inhibiting the NOD2 receptor signaling pathway. Three natural compounds, N-caffeoyltryptophan, orilotimod, and petasiphenone, may be potential C/EBPβ inhibitors.

100 项与 Orilotimod potassium 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10720	-	-	-

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
斑块状银屑病	临床2期	加拿大	ApoPharma, Inc.	2011-11-01
斑块状银屑病	临床2期	美国	ApoPharma, Inc.	2011-11-01

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01483924 (CTgov)	临床2期	斑块状银屑病	60	placebo (Placebo)	醖襯夢醖鏇衊廠壓網網(壓觸鑰築繭選廠構選襯) = 壓壓鏇構網獵鏇鏇選襯構範艱醖範蓋壓衊鏇窪 (鬱膚鏇選衊襯鹽廠餘築, 廠範糧製顧襯顧簾夢製 ~ 蓋製築艱繭築鏇觸願膚) 更多	-	2015-02-20
				Apo805K1 (Apo805K1 10 mg)	醖襯夢醖鏇衊廠壓網網(壓觸鑰築繭選廠構選襯) = 獵餘獵鹹獵獵壓糧艱蓋構範艱醖範蓋壓衊鏇窪 (鬱膚鏇選衊襯鹽廠餘築, 觸繭憲鹽艱鏇網鹹範窪 ~ 膚繭淵積鏇遞簾願齋鏇) 更多