Ulimorelin(Ulimorelin) - 药物靶点：GHSR_专利_临床

概要

基本信息

药物类型

合成多肽

别名

LP 101、TZP-101

靶点

GHSR

作用方式

激动剂

作用机制

GHSR激动剂(促生长激素释放激素受体激动剂)

治疗领域

消化系统疾病

在研适应症-

非在研适应症

术后肠梗阻

原研机构

广州凌腾生物医药有限公司

在研机构-

非在研机构

Norgine Ltd.

权益机构

Norgine Europe BV

OCERA Therapeutics LLC

最高研发阶段无进展临床3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

分子式C30H39FN4O4

InChIKeyWGYPAJVJMXQXTR-ABNZCKJZSA-N

CAS号842131-33-3

关联

13

项与 Ulimorelin 相关的临床试验

NCT02784392

/ Completed临床2期

A Phase 2, Multicenter, Randomized, Double-Blind, Comparator-Controlled Study of the Efficacy, Safety, and Pharmacokinetics of Intravenous Ulimorelin (LP101) in Patients With Enteral Feeding Intolerance (EFI)

The purpose of this study is to evaluate the effect Ulimorelin in patients with enteral feeding intolerance.

开始日期2016-10-01

申办/合作机构

Lyric Pharmaceuticals, Inc.

NCT02993055

/ Completed临床1期

A Phase I, Randomised, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Ulimorelin (LP101)

A Phase I dose escalation study involving healthy subjects.

开始日期2015-01-01

申办/合作机构

Lyric Pharmaceuticals, Inc.

EUCTR2011-004474-29-CZ

/ Not yet recruitingN/A

A Multicentre, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Safety of TZP-101 (IV Ulimorelin) Administered Post-Operatively in Patients Who Have Undergone Partial Bowel Resection - SDS

开始日期2012-03-02

申办/合作机构

Norgine Ltd.

100 项与 Ulimorelin 相关的临床结果

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100 项与 Ulimorelin 相关的转化医学

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100 项与 Ulimorelin 相关的专利（医药）

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40

项与 Ulimorelin 相关的文献（医药）

2023-12-29·Canadian journal of gastroenterology & hepatology

Ghrelin/GHSR Axis Induced M2 Macrophage and Alleviated Intestinal Barrier Dysfunction in a Sepsis Rat Model by Inactivating E2F1/NF-κB Signaling

Article

作者: Hou, Qiliang ; Yuan, Ziqian ; Zhu, Lei ; Wang, Sen ; Liu, Jian ; Wu, Wei ; Dou, Zhimin ; Li, Bin

Sepsis is an inflammatory reaction disorder state that is induced by infection. The activation and regulation of the immune system play an essential role in the development of sepsis. Our previous studies have shown that ghrelin ameliorates intestinal dysfunction in sepsis. Very little is known about the mechanism of ghrelin and its receptor (GHSR) on the intestinal barrier and the immune function of macrophage regulation. Our research is to investigate the regulatory effect and molecular mechanism of the ghrelin/GHSR axis on intestinal dysfunction and macrophage polarization in septic rats. A rat model of sepsis was established by cecal ligation and puncture (CLP) operation. Then, the sepsis rats were treated with a ghrelin receptor agonist (TZP-101) or ghrelin inhibitor (obestatin). The results suggested that TZP-101 further enhanced ghrelin and GHSR expressions in the colon and spleen of septic rats and obestatin showed the opposite results. Ghrelin/GHSR axis ameliorated colonic structural destruction and intestinal epithelial tight junction injury in septic rats. In addition, the ghrelin/GHSR axis promoted M2-type polarization of macrophages, which was characterized by the decreases of IL-1β, IL-6, and TNF-α, as well as the increase of IL-10. Mechanistically, the ghrelin/GHSR axis promoted E2F2 expression and suppressed the activation of the NF-κB signaling pathway in septic rats. Collectively, targeting ghrelin/GHSR during sepsis may represent a novel therapeutic approach for the treatment of intestinal barrier injury.

2020-03-01·Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society3区 · 医学

The effects of ulimorelin, a ghrelin agonist, on liquid gastric emptying and colonic transit in humans

3区 · 医学

Article

作者: Maurer, Alan ; Deane, Adam M ; Doll, Walter ; Harris, M. Scott ; Mair, Stuart ; Wurtman, David ; James, Joyce ; Sandefer, Erik

Abstract:

Background:

Ulimorelin, a small molecule ghrelin agonist and prokinetic agent, was effective in animal models of gastroparesis and delayed transit. However, employing once daily administration, it failed in clinical trials of postoperative ileus (POI), a condition in which colonic motility recovers last. The aim of this study was to evaluate drug dosing and regional differences in drug activity between stomach and colon.

Methods:

Gastric emptying was assessed by scintigraphy in healthy adults at single doses of 600‐1200 µg kg−1 and multiple doses of 80‐600 µg kg−1 Q8H for 7 days. Colonic motility was assessed by 7‐region scintigraphic analysis at a dose of 600 µg kg−1 for 2 days. The primary endpoints were percent change in time to 50% (∆t50) liquid gastric emptying on Days 1, 4, and 6 and the geometric mean center of colonic transit at 24 hours (GC24). Plasma concentrations of free and total ulimorelin were measured for pharmacokinetic and exposure‐response modeling.

Key Results:

Ulimorelin 150‐600 µg kg−1 every 8 hours resulted in statistically significant improvements (∆t50 = 23% to 46% (P < .05)) in gastric emptying from baseline that were sustained through Day 6. However, no effects on GC24 were observed. Pharmacokinetic analyses suggested that the free concentrations of ulimorelin achieved in POI trials and dosing frequency may have been inadequate.

Conclusions and Inferences:

Ulimorelin is a potent gastric prokinetic but lacks evidence of activity in the human colon, pointing to the stomach as the predominant site of action of ghrelin in humans; ClinicalTrials.gov NCT02993055.

2019-05-01·Intensive care medicine1区 · 医学

A multicenter, randomized, double-blind study of ulimorelin and metoclopramide in the treatment of critically ill patients with enteral feeding intolerance: PROMOTE trial

1区 · 医学

Article

作者: Serviá-Goixart, Lluis ; van Zanten, Arthur ; Stelfox, Tom ; Calvo-Herranz, Enrique ; van Zanten, Arthur R. H. ; Wilhelmina, Canisius ; Cervera, Manuel ; Harris, M. Scott ; Garcia-Martinez, Miguel Angel ; Gonzalez, Jesus ; Heyland, Daren K. ; Raines, Ronald ; Yébenes-Reyes, Juan Carlos ; Posadas, Juan ; Klein, David J. ; Peredes, Amparo ; Fernadez-Ortega, Juan Franscisco ; Grau-Carmona, Teodoro ; Hoiting, Oscar ; Fernández-González, Inmaculada ; Jolley, Sarah ; Perez-Quesada, Sonia ; Evans, David ; Bordejé, Maria Luisa ; Perez, Aitor ; Beishuizen, Albertus ; Krell, Kenneth ; James, Joyce ; Herrero-Meseguer, Jose Ignacio ; Falls, Idaho ; Brown, Randy ; Evans, David C. ; Lorencio, Carol ; Schouten, Jeroen

PURPOSE:

Enteral feeding intolerance (EFI) is a frequent problem in the intensive care unit (ICU), but current prokinetic agents have uncertain efficacy and safety profiles. The current study compared the efficacy and safety of ulimorelin, a ghrelin agonist, with metoclopramide in the treatment of EFI.

METHODS:

One hundred twenty ICU patients were randomized 1:1 to ulimorelin or metoclopramide for 5 days. EFI was diagnosed by a gastric residual volume (GRV) ≥ 500 ml. A volume-based feeding protocol was employed, and enteral formulas were standardized. The primary end point was the percentage daily protein prescription (%DPP) received by patients over 5 days of treatment. Secondary end points included feeding success, defined as 80% DPP; gastric emptying, assessed by paracetamol absorption; incidences of recurrent intolerance (GRV ≥ 500 ml); vomiting or regurgitation; aspiration, defined by positive tracheal aspirates for pepsin; and pulmonary infection.

RESULTS:

One hundred twenty patients were randomized and received the study drug (ulimorelin 62, metoclopramide 58). Mean APACHE II and SOFA scores were 21.6 and 8.6, and 63.3% of patients had medical reasons for ICU admission. Ulimorelin and metoclopramide resulted in comparable %DPPs over 5 days of treatment (median [Q1, Q3]: 82.9% [38.4%, 100.2%] and 82.3% [65.6%, 100.2%], respectively, p = 0.49). Five-day rates of feeding success were 67.7% and 70.6% when terminations unrelated to feeding were excluded, and there were no differences in any secondary outcomes or adverse events between the two groups.

CONCLUSIONS:

Both prokinetic agents achieved similar rates of feeding success, and no safety differences between the two treatment groups were observed.

100 项与 Ulimorelin 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Ulimorelin	-	DB12128

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
术后肠梗阻	临床3期	-	Norgine Ltd.	2012-02-01

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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


NCT02784392 (PROMOTE, Pubmed \| Intensive Care Med) 人工标引	临床2期	危重病	120	ulimorelin	製遞簾醖醖鹹憲範糧簾(鏇繭膚鏇鑰積鬱鹽艱夢) = 築糧網蓋簾構廠選蓋夢衊膚網襯蓋鏇製構獵遞 (構蓋餘壓遞製齋鑰艱築 ) 更多	积极	2019-05-01
				metoclopramide	製遞簾醖醖鹹憲範糧簾(鏇繭膚鏇鑰積鬱鹽艱夢) = 淵鏇鹽積艱鏇製顧壓衊衊膚網襯蓋鏇製構獵遞 (構蓋餘壓遞製齋鑰艱築 ) 更多