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

作用方式

抑制剂

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.

权益机构-

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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2

项与 LY-2928057 相关的文献（医药）

2019-05-01·British Journal of Clinical Pharmacology2区 · 医学

Targeting the hepcidin–ferroportin pathway in anaemia of chronic kidney disease

2区 · 医学

Article

作者: Benschop, Robert ; Berg, Jolene ; Berg, Paul H. ; Decker, Brian ; Leung, Donmienne ; McColm, Juliet ; Barrington, Philip ; Sheetz, Matthew ; Marbury, Thomas ; Callies, Sophie ; Truhlar, Stephanie M.E. ; Witcher, Derrick R. ; Dyas, Gregory L.

AimsErythropoiesis‐stimulating agents used to treat anaemia in patients with chronic kidney disease (CKD) have been associated with cardiovascular adverse events. Hepcidin production, controlled by bone morphogenic protein 6 (BMP6), regulates iron homeostasis via interactions with the iron transporter, ferroportin. High hepcidin levels are thought to contribute to increased iron sequestration and subsequent anaemia in CKD patients. To investigate alternative therapies to erythropoiesis‐stimulating agents for CKD patients, monoclonal antibodies, LY3113593 and LY2928057, targeting BMP6 and ferroportin respectively, were tested in CKD patients.MethodsPreclinical in vitro/vivo data and clinical data in healthy subjects and CKD patients were used to illustrate the translation of pharmacological properties of LY3113593 and LY2928057, highlighting the novelty of targeting these nodes within the hepcidin–ferroportin pathway.ResultsLY2928057 bound ferroportin and blocked interactions with hepcidin, allowing iron efflux, leading to increased serum iron and transferrin saturation levels and increased hepcidin in monkeys and humans. In CKD patients, LY2928057 led to slower haemoglobin decline and reduction in ferritin (compared to placebo). Serum iron increase was (mean [90% confidence interval]) 1.98 [1.46–2.68] and 1.36 [1.22–1.51] fold‐relative to baseline following LY2928057 600 mg and LY311593 150 mg respectively in CKD patients. LY3113593 specifically blocked BMP6 binding to its receptor and produced increases in iron and transferrin saturation and decreases in hepcidin preclinically and clinically. In CKD patients, LY3113593 produced an increase in haemoglobin and reduction in ferritin (compared to placebo).ConclusionLY3113593 and LY2928057 pharmacological effects (serum iron and ferritin) were translated from preclinical‐to‐clinical development. Such interventions may lead to new CKD anaemia treatments.

Scientific Reports3区 · 综合性期刊

The Hepcidin/Ferroportin axis modulates proliferation of pulmonary artery smooth muscle cells

3区 · 综合性期刊

ArticleOA

作者: Pedersen, Sofia L ; Mumby, Sharon ; Wort, S John ; Quinlan, Gregory J ; Toe, Quezia K ; Garfield, Benjamin ; Ramakrishnan, Latha ; West, Laura E ; Casbolt, Helen ; Lawrie, Allan ; Issitt, Theo

AbstractStudies were undertaken to examine any role for the hepcidin/ferroportin axis in proliferative responses of human pulmonary artery smooth muscle cells (hPASMCs). Entirely novel findings have demonstrated the presence of ferroportin in hPASMCs. Hepcidin treatment caused increased proliferation of these cells most likely by binding ferroportin resulting in internalisation and cellular iron retention. Cellular iron content increased with hepcidin treatment. Stabilisation of ferroportin expression and activity via intervention with the therapeutic monoclonal antibody LY2928057 reversed proliferation and cellular iron accumulation. Additionally, IL-6 treatment was found to enhance proliferation and iron accumulation in hPASMCs; intervention with LY2928057 prevented this response. IL-6 was also found to increase hepcidin transcription and release from hPASMCs suggesting a potential autocrine response. Hepcidin or IL-6 mediated iron accumulation contributes to proliferation in hPASMCs; ferroportin mediated cellular iron excretion limits proliferation. Haemoglobin also caused proliferation of hPASMCs; in other novel findings, CD163, the haemoglobin/haptoglobin receptor, was found on these cells and offers a means for cellular uptake of iron via haemoglobin. Il-6 was also found to modulate CD163 on these cells. These data contribute to a better understanding of how disrupted iron homeostasis may induce vascular remodelling, such as in pulmonary arterial hypertension.

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)	顧衊鬱鏇鏇築糧膚願遞(蓋顧襯襯網顧餘衊襯觸) = 築鬱壓構襯廠淵鏇膚艱鹹蓋選齋鹹鑰選憲製鹹 (範餘網獵糧窪餘廠築艱, 膚鏇膚鏇鏇構鬱範構鬱 ~ 繭醖顧齋簾糧醖壓築壓) 更多	-	2019-02-07
				LY2928057 (300 mg LY2928057)	顧衊鬱鏇鏇築糧膚願遞(蓋顧襯襯網顧餘衊襯觸) = 鑰遞鹹製獵壓鬱簾夢簾鹹蓋選齋鹹鑰選憲製鹹 (範餘網獵糧窪餘廠築艱, 簾繭膚願膚餘醖網範積 ~ 餘壓鬱積鹹願鬱襯積醖) 更多
NCT01330953 (CTgov)	临床1期	-	32	Placebo	襯齋餘衊壓鹹蓋鬱鑰選(遞網構鑰廠鑰構淵範簾) = 窪糧膚糧簾憲範淵膚顧憲衊簾鏇鬱鏇蓋積鏇襯 (積鑰蓋鑰製繭窪鏇蓋獵, 選廠窪鏇觸艱觸鹹襯襯 ~ 觸鬱蓋選網鹹鹹網獵範) 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	(鏇衊壓淵選鑰襯衊鏇淵) = 窪繭夢範鬱蓋夢觸鏇簾簾選獵觸艱鬱醖餘積範 (鹹製蓋製範淵積齋觸餘 ) 更多	积极	2016-12-02
				placebo	-