LY-2928057(LY-2928057) - 药物靶点：FPN1_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Anti-ferroportin antibody

靶点

FPN1

作用机制

FPN1抑制剂(膜铁转运蛋白-1抑制剂)

治疗领域

泌尿生殖系统疾病

在研适应症-

非在研适应症

慢性肾病

原研机构

Eli Lilly & Co.

在研机构-

非在研机构

Eli Lilly & Co.

最高研发阶段无进展临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

Sequence Code 1116885922L

Sequence Code 129827H

关联

2

项与 LY-2928057 相关的临床试验

NCT01991483

/ Completed临床1期

A Multiple-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY2928057 in Hemodialysis Patients

This study will evaluate the safety of LY2928057 and how LY2928057 affects hemoglobin in hemodialysis participants. This study will involve multiple doses of LY2928057 given during a 6 week period either after a participant discontinues or reduces treatment to stimulate red blood cells. This study will last up to 26 weeks for each participant.

开始日期2013-12-01

申办/合作机构

Eli Lilly & Co.

NCT01330953

/ Completed临床1期

A Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY2928057 in Healthy Subjects

The purposes of this study are to evaluate the following in healthy participants: 1) LY2928057 safety, including any side effects possibly associated with LY2928057; 2) how the body processes LY2928057; 3) effect of LY2928057 on blood iron levels; and 4) immune system reactions to LY2928057.

开始日期2011-03-01

申办/合作机构

Eli Lilly & Co.

100 项与 LY-2928057 相关的临床结果

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100 项与 LY-2928057 相关的转化医学

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100 项与 LY-2928057 相关的专利（医药）

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14

项与 LY-2928057 相关的文献（医药）

2024-09-01·HemaSphere

The oral ferroportin inhibitor vamifeport prevents liver iron overload in a mouse model of hemochromatosis

Article

作者: Altermatt, Patrick ; Nyffenegger, Naja ; Flace, Anna ; Sundstrom, Hanna ; Manolova, Vania ; Varol, Ahmet ; Doucerain, Cédric ; Dürrenberger, Franz

AbstractHemochromatosis is an inherited iron overload condition caused by mutations that reduce the levels of the iron‐regulatory hormone hepcidin or its binding to ferroportin. The hepcidin–ferroportin axis is pivotal to iron homeostasis, providing opportunities for therapeutic intervention in iron overload disorders like hemochromatosis. The aim of this study was to evaluate the efficacy of the oral ferroportin inhibitor vamifeport in the Hfe C282Y mouse model, which carries the most common mutation found in patients with hemochromatosis. A single oral dose of vamifeport lowered serum iron levels in Hfe C282Y mice, with delayed onset and shorter duration than observed in wild‐type mice. Vamifeport induced transient hypoferremia by inhibiting ferroportin and resulted in a feedback regulation of liver Hamp in wild‐type mice, which was absent in Hfe C282Y mice, reflecting the dysregulated systemic iron sensing in this hemochromatosis model. Chronic dosing with vamifeport led to sustained serum and liver iron reductions in Hfe C282Y mice, as well as markedly reducing liver Hamp expression in Hfe C282Y mice, suggesting distinct regulation of liver Hamp expression following acute or continuous iron restriction via vamifeport. At the tested dose, vamifeport retained its activity when combined with phlebotomy and did not significantly interfere with liver iron removal by phlebotomy in Hfe C282Y mice. These data demonstrate that chronic vamifeport treatment significantly reduces serum iron levels and prevents liver iron loading in the Hfe C282Y mouse model of hemochromatosis, thus providing preclinical proof of concept for the efficacy of vamifeport in hemochromatosis with or without phlebotomy.

2023-10-01·Haematologica

Ferroportin inhibitor vamifeport ameliorates ineffective erythropoiesis in a mouse model of β-thalassemia with blood transfusions.

Article

作者: Altermatt, Patrick ; Nyffenegger, Naja ; Flace, Anna ; Dürrenberger, Franz ; Kalleda, Natarajaswamy ; Doucerain, Cédric ; Ingoglia, Giada ; Manolova, Vania

β-thalassemia is an inherited anemia characterized by ineffective erythropoiesis. Blood transfusions are required for survival in transfusion-dependent β-thalassemia and are also occasionally needed in patients with non-transfusion-dependent β-thalassemia. Patients with transfusion-dependent b-thalassemia often have elevated transferrin saturation (TSAT) and non-transferrin-bound iron (NTBI) levels, which can lead to organ iron overload, oxidative stress, and vascular damage. Vamifeport is an oral ferroportin inhibitor that was previously shown to ameliorate anemia, ineffective erythropoiesis, and dysregulated iron homeostasis in the Hbbth3/+ mouse model of β-thalassemia, under non-transfused conditions. Our study aimed to assess the effects of oral vamifeport on iron-related parameters (including plasma NTBI levels) and ineffective erythropoiesis following blood transfusions in Hbbth3/+ mice. A single dose of vamifeport prevented the transient transfusion-mediated NTBI increase in Hbbth3/+ mice. Compared with vehicle treatment, vamifeport significantly increased hemoglobin levels and red blood cell counts in transfused mice. Vamifeport treatment also significantly improved ineffective erythropoiesis in the spleens of Hbbth3/+ mice, with additive effects observed when treatment was combined with repeated transfusions. Vamifeport corrected leukocyte counts and significantly improved iron-related parameters (serum transferrin, TSAT and erythropoietin levels) versus vehicle treatment in Hbbth3/+ mice, irrespective of transfusion status. In summary, vamifeport prevented transfusion-mediated NTBI formation in Hbbth3/+ mice. When given alone or combined with blood transfusions, vamifeport also ameliorated anemia, ineffective erythropoiesis, and dysregulated iron homeostasis. Administering vamifeport together with repeated blood transfusions additively ameliorated anemia and ineffective erythropoiesis in this mouse model, providing preclinical proof-of-concept for the efficacy of combining vamifeport with blood transfusions in β-thalassemia.

2022-08-18·Blood

The oral ferroportin inhibitor vamifeport improves hemodynamics in a mouse model of sickle cell disease

Article

作者: Doucerain, Cédric ; Flace, Anna ; Dürrenberger, Franz ; Buehler, Paul W. ; Nyffenegger, Naja ; Ingoglia, Giada ; Zennadi, Rahima ; Manolova, Vania ; Kalleda, Natarajaswamy ; Buzzi, Raphael M. ; Schaer, Dominik J.

AbstractSickle cell disease (SCD) is an inherited hemolytic anemia caused by a single point mutation in the β-globin gene of hemoglobin that leads to synthesis of sickle hemoglobin (HbS) in red blood cells (RBCs). HbS polymerizes in hypoxic conditions, leading to intravascular hemolysis, release of free hemoglobin and heme, and increased adhesion of blood cells to the endothelial vasculature, which causes painful vaso-occlusion and organ damage. HbS polymerization kinetics are strongly dependent on the intracellular HbS concentration; a relatively small reduction in cellular HbS concentration may prevent HbS polymerization and its sequelae. We hypothesized that iron restriction via blocking ferroportin, the unique iron transporter in mammals, might reduce HbS concentration in RBCs, thereby decreasing hemolysis, improving blood flow, and preventing vaso-occlusive events. Indeed, vamifeport (also known as VIT-2763), a clinical-stage oral ferroportin inhibitor, reduced hemolysis markers in the Townes model of SCD. The RBC indices of vamifeport-treated male and female Townes mice exhibited changes attributable to iron-restricted erythropoiesis: decreased corpuscular hemoglobin concentration mean and mean corpuscular volume, as well as increased hypochromic and microcytic RBC fractions. Furthermore, vamifeport reduced plasma soluble VCAM-1 concentrations, which suggests lowered vascular inflammation. Accordingly, intravital video microscopy of fluorescently labeled blood cells in the microvasculature of Townes mice treated with vamifeport revealed diminished adhesion to the endothelium and improved hemodynamics. These preclinical data provide a strong proof-of-concept for vamifeport in the Townes model of SCD and support further development of this compound as a potential novel therapy in SCD.

100 项与 LY-2928057 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
慢性肾病	临床1期	美国	Eli Lilly & Co.	2013-12-01

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临床结果

适应症

分期

评价

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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


NCT01991483 (CTgov)	临床1期	慢性肾病	28	Placebo (Placebo)	網選獵觸積製簾衊製鹽(鏇醖鏇遞範膚窪選艱製) = 艱齋範獵遞顧夢齋網膚憲廠鑰顧齋積觸夢醖鬱 (鑰鹽製觸築襯齋願餘積, 網遞憲繭醖鬱醖廠壓鹹 ~ 衊顧繭憲憲廠構選網鏇) 更多	-	2019-02-07
				LY2928057 (300 mg LY2928057)	網選獵觸積製簾衊製鹽(鏇醖鏇遞範膚窪選艱製) = 鹹醖繭餘齋製簾鹹鹹憲憲廠鑰顧齋積觸夢醖鬱 (鑰鹽製觸築襯齋願餘積, 鹽憲鬱襯製鬱蓋網積製 ~ 鬱構醖積壓鹽選憲網觸) 更多
NCT01330953 (CTgov)	临床1期	-	32	Placebo	淵鬱積憲鏇鬱構餘餘網(齋選艱繭觸壓窪選選鹽) = 廠範範膚餘範遞築鑰膚淵觸選鹽積選糧窪餘遞 (醖鑰鹹願襯網齋窪鏇遞, 築遞壓壓壓築鹽醖鏇獵 ~ 鑰願餘衊淵選鹽簾廠蓋) 更多	-	2018-07-30
NCT01991483 (ASH 12016 \| ASH 22016) 人工标引	临床1期	终末期肾脏病	28	LY 2928057	(遞艱積膚製範淵蓋構窪) = 糧選遞齋鹹壓淵窪憲夢製膚夢願遞壓艱積網積 (築觸餘餘簾鹹衊觸顧繭 ) 更多	积极	2016-12-02
				placebo	-