Effect of antifibrotic therapy on regression of myocardial fibrosis after transcatheter aortic valve implantation (TAVI) in aortic stenosis patients with high fibrotic burden

开始日期2022-03-21

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100 项与 Interleukin 11 Antagonist(Boehringer Ingelheim) 相关的临床结果

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100 项与 Interleukin 11 Antagonist(Boehringer Ingelheim) 相关的转化医学

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100 项与 Interleukin 11 Antagonist(Boehringer Ingelheim) 相关的专利（医药）

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项与 Interleukin 11 Antagonist(Boehringer Ingelheim) 相关的文献（医药）

2025-04-24·Journal of Medicinal Chemistry

Development of a Long-Acting Interleukin-11 Antagonist for the Treatment of Renal Fibrosis

Article

作者: Cheng, Xing ; Pang, Ningning ; Xiong, Xiaochun ; Zhao, Na ; Li, Jian ; Wang, Naiyuan ; Zheng, Nan ; Li, Keqiang ; Li, Peiying ; An, Chunmei ; Guo, Dong

Renal fibrosis, a key progression of chronic kidney disease (CKD), remains a major challenge in nephrology, with no FDA-approved drugs specifically targeting this condition. Interleukin-11 (IL-11) has emerged as a potential therapeutic target for renal fibrosis. In this study, we identified the antifibrotic effects of a recombinant human IL-11 analogue, IL-11-6M, in a mouse model of unilateral ureteral obstruction (UUO). We generated additional IL-11-6M variants via an optimized Escherichia coli expression system, with one variant (D46C) exhibiting comparable efficacy. Further modified through cysteine-specific PEGylation, analogue 13 demonstrated similar potency to IL-11-6M with an IC₅₀ value of 61.5 ± 26.2 nM and maintained strong binding affinity to IL-11Rα (K_D = 3.0 nM). Notably, analogue 13 exhibited a prolonged half-life and showed significant therapeutic effects in the UUO-induced renal fibrosis model. These findings suggest analogue 13 should be a promising candidate for the treatment of renal fibrosis.

2021-05-01·Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology

[Effects of interleukin-11 antagonist on pulmonary fibrosis in mice].

Article

作者: Wu, Li Xun ; Wu, Xiang

目的: 观察拮抗白介素11(IL-11)对博来霉素(BLM)诱导的实验性小鼠肺纤维化的作用。方法: 将120只雄性C57BL/6小鼠随机分为正常对照组、IL-11拮抗剂组、BLM组和BLM+IL-11拮抗剂组(每组各30只)。BLM组和BLM+ IL-11拮抗剂组小鼠一次性气管注射BLM(1.5 mg/kg)诱导肺纤维化。于造模当日开始,IL-11拮抗剂组和BLM+IL-11拮抗剂组小鼠每间隔3 d尾静脉注射IL-11拮抗剂IL-11 Rα FC(2.5 mg/kg)。观察各组小鼠生存状态。于造模后第21日取肺组织进行HE染色、Masson染色以及Ashcroft评分评价肺纤维化程度。通过碱水解法测定肺组织中羟脯氨酸(HYP)的含量;采用Real-time PCR和Western blot检测肺组织中Collagen I、Collagen III和α-SMA 的基因和蛋白表达;采用酶联免疫吸附法测定肺组织中TGF-β1含量。结果: 与正常对照组相比,BLM可降低小鼠存活率(P＜0.05),破坏肺组织结构,导致大量胶原沉积,显著升高HYP含量、肺组织中Collagen I、Collagen III和α-SMA的基因和蛋白表达(P＜0.05),以及TGF-β1含量(P＜0.05)。而IL-11 Rα Fc处理可改善肺纤维小鼠的生存率,减轻肺组织病理学改变以及胶原沉积,减少肺组织中HYP含量(P＜0.05),下调肺组织中Collagen I、Collagen III和α-SMA的基因和蛋白表达(P＜0.05),以及TGF-β1含量(P＜0.05)。结论: IL-11拮抗剂可减轻BLM诱导的小鼠肺纤维化,为临床治疗肺纤维化提供了新思路。.

2003-08-01·Endocrinology2区 · 医学

Functional Characterization of W147A: A High-Affinity Interleukin-11 Antagonist

2区 · 医学

Article

作者: Underhill-Day, Nicholas ; Barton, Victoria A. ; McGovern, Lisa A. ; Mardon, Helen J. ; Karpovich, Natalia ; Heath, John K.

IL-11 is a member of the gp130 family of cytokines, which signal via assembly of multisubunit receptor complexes containing at least one molecule of the transmembrane signaling receptor gp130. IL-11 forms a high-affinity complex, thereby inducing gp130-dependent signaling. Previous studies have identified three distinct receptor binding sites, I, II, and III, crucial for the binding of murine IL-11 (mIL-11) to both the IL-11R and gp130. In this study, we have further characterized the role of the mIL-11 site III mutant W147A. We show that W147A is a high-affinity specific antagonist of mIL-11-mediated signaling in gp130/IL-11R-transfected Ba/F3 cells. The antagonistic action of W147A is due to its ability to competitively disrupt multimeric gp130/IL-11R signaling complex formation. We also show that W147A inhibits IL-11-mediated signaling in primary human endometrial cells, thus demonstrating the potential utility of W147A in suppressing IL-11 responses in vivo.

100 项与 Interleukin 11 Antagonist(Boehringer Ingelheim) 相关的药物交易

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