LAT-8881(LAT-8881) - 药物靶点：GHR_在研适应症：腰椎神经根病，根性疼痛_专利_临床

概要

基本信息

药物类型

化学药

别名

靶点

GHR

作用方式

激动剂

作用机制

GHR激动剂(生长激素受体激动剂)

治疗领域

神经系统疾病其他疾病

在研适应症

腰椎神经根病根性疼痛

非在研适应症

急性偏头痛糖尿病周围神经病变疱疹后神经痛+ [2]

原研机构

Mesoestetic Sl

在研机构

Lateral Pharma Pty Ltd.

非在研机构

Metabolic Pharmaceuticals Pty Ltd.

最高研发阶段临床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

分子式C78H123N23O23S2

InChIKeyGVIYUKXRXPXMQM-BPXGDYAESA-N

CAS号221231-10-3

Sequence Code 86160

来源: *****

关联

5

项与 LAT-8881 相关的临床试验

NCT05298306

/ Completed临床1期

A Two-part Proof-of-Concept Study Assessing the Safety and Efficacy of LAT8881 in Lumbar Radicular Pain

The study consists of two parts. Part A will evaluate the safety and tolerability of intravenous LAT8881 in healthy volunteers using an ascending dose schedule. Part B will evaluate the analgesic efficacy of a single intravenous dose of LAT8881, compared with placebo, in patients with lumbar radicular pain.
Healthy volunteers are not accepted for Part B.

开始日期2022-05-17

申办/合作机构

Lateral Pharma Pty Ltd.

[+1]

ACTRN12619001369112

/ Completed临床2期

A proof of concept study of the efficacy and safety of oral LAT8881 in acute migraine

开始日期2019-10-04

申办/合作机构

Lateral Pharma Pty Ltd.

NCT04153409

/ Completed临床2期

A Proof of Concept Study of the Efficacy and Safety of Oral LAT8881 in Acute Migraine

This is a randomised, placebo controlled, double blind, crossover proof of concept study to investigate the efficacy and safety of oral LAT8881 in acute migraine, with or without aura.

开始日期2019-09-24

申办/合作机构

Lateral Pharma Pty Ltd.

100 项与 LAT-8881 相关的临床结果

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100 项与 LAT-8881 相关的转化医学

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100 项与 LAT-8881 相关的专利（医药）

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39

项与 LAT-8881 相关的文献（医药）

2024-08-16·The Journal of Infectious Diseases

Harnessing Endogenous Peptide Compounds as Potential Therapeutics for Severe Influenza

Article

作者: Tate, Michelle D ; Ely, Lauren K ; Hodges, Christopher ; West, Alison C ; Harpur, Christopher M ; Lam, Maggie ; Le Page, Mélanie A ; Gearing, Andrew J

AbstractBackgroundExcessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic 16–amino acid cyclic peptide form of a naturally occurring C-terminal fragment of human growth hormone with therapeutic efficacy against influenza. Shorter linear peptides are typically easier to manufacture and formulate for delivery than larger cyclic peptides. A 6–amino acid linear peptide fragment of LAT8881, LAT9997, was investigated as a potential influenza therapy.MethodsLAT9997 was evaluated for its potential to limit disease in a preclinical mouse model of severe influenza infection.ResultsIntranasal treatment of mice with either LAT8881 or LAT9997 from day 1 following influenza infection significantly improved survival outcomes. Initiating LAT9997 treatment at the onset of severe disease also significantly improved disease severity. Greater disease resistance in LAT9997-treated mice correlated with reduced lung immunopathology, damage markers, vascular leak, and epithelial cell death. Treatment reduced viral loads, cytokines, and neutrophil infiltration in the airways yet maintained protective alveolar macrophages in a dose-dependent manner. Sequential trimming of N- and C-terminal amino acids from LAT9997 revealed a structure-activity relationship.ConclusionsThese findings provide preclinical evidence that therapeutic LAT9997 treatment limits viral burden and characteristic features of severe influenza, including hyperinflammation and lung damage.SummaryExcessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT9997 is a linear peptide fragment derived from human growth hormone. This study provides preclinical evidence that therapeutic LAT9997 treatment limits viral burden, hyperinflammation, and lung damage.

2023-01-01·Clinical & Translational Immunology

Naturally derived cytokine peptides limit virus replication and severe disease during influenza A virus infection

Article

作者: Tate, Michelle D ; Harpur, Christopher M ; Hodges, Christopher ; Oseghale, Osezua ; Lam, Maggie ; Le Page, Mélanie A ; West, Alison C ; Gearing, Andrew J

AbstractObjectivesNovel host‐targeted therapeutics could treat severe influenza A virus (IAV) infections, with reduced risk of drug resistance. LAT8881 is a synthetic form of the naturally occurring C‐terminal fragment of human growth hormone. Acting independently of the growth hormone receptor, it can reduce inflammation‐induced damage and promote tissue repair in an animal model of osteoarthritis. LAT8881 has been assessed in clinical trials for the treatment of obesity and neuropathy and has an excellent safety profile. We investigated the potential for LAT8881, its metabolite LAT9991F and LAT7771 derived from prolactin, a growth hormone structural homologue, to treat severe IAV infection.MethodsLAT8881, LAT9991F and LAT7771 were evaluated for their effects on cell viability and IAV replication in vitro, as well as their potential to limit disease in a preclinical mouse model of severe IAV infection.ResultsIn vitro LAT8881 treatment enhanced cell viability, particularly in the presence of cytotoxic stress, which was countered by siRNA inhibition of host lanthionine synthetase C‐like proteins. Daily intranasal treatment of mice with LAT8881 or LAT9991F, but not LAT7771, from day 1 postinfection significantly improved influenza disease resistance, which was associated with reduced infectious viral loads, reduced pro‐inflammatory cytokines and increased abundance of protective alveolar macrophages. LAT8881 treatment in combination with the antiviral oseltamivir phosphate led to more pronounced reduction in markers of disease severity than treatment with either compound alone.ConclusionThese studies provide the first evidence identifying LAT8881 and LAT9991F as novel host‐protective therapies that improve survival, limit viral replication, reduce local inflammation and curtail tissue damage during severe IAV infection. Evaluation of LAT8881 and LAT9991F in other infectious and inflammatory conditions of the airways is warranted.

2022-08-01·Journal of Chromatography A

Multi-analyte screening of small peptides by alkaline pre-activated solid phase extraction coupled with liquid chromatography-high resolution mass spectrometry in doping controls

Article

作者: Tian, Tian ; Jing, Jing ; Xu, Xin ; Shan, Yuanhong ; Wang, Yang

Peptidic drugs with wide spectrum of physiological activity are of interest for cheating athletes and can be misused as doping in sports. A growing number of small peptide drugs capable of enhancing performance are included in the prohibited list issued by World Anti-Doping Agency (WADA), therefore the improvement of the detection methods is constantly needed. In the present study, a screening assay was developed comprising 54 prohibited small peptides and the related substances in urine by means of the alkaline pre-activated weak cation exchange-solid phase extraction (WCX-SPE) with liquid chromatography-high resolution mass spectrometry (LCHRMS). This method performed good enrichment and purification effect of traditional WCX for basic peptides, and also improve the purification power of acidic peptides, which significantly expanded the coverage of detection substances. The method was validated in accordance with WADA relevant criteria and validated with a main focus on qualitative parameters including selectivity, limits of detection (0.02-0.2 ng/mL), linearity (0.1-20 ng/mL for 46 analytes and 0.2-20 ng/mL for 9 analytes), accuracy and precision (RE% and RSD% < 20% at 1, 5 and 10 ng/mL), recovery (39.2%-100.1% except for the TB500(1-2) free acid: 9.2%), matrix effects (ion suppression effect: 0 to 49.4% and ion enhancement effect: 100% and 264.6%), carryover, reliability and sample extract stability. As a proof-of-principle, urine samples from two patients received a single injection of leuprorelin acetate microspheres (3.75 mg) 30 days before were analyzed and the results proved the applicability of the method.

100 项与 LAT-8881 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
急性偏头痛	临床2期	澳大利亚	Lateral Pharma Pty Ltd.	2019-09-24
糖尿病周围神经病变	临床2期	澳大利亚	Lateral Pharma Pty Ltd.	2019-04-09
糖尿病周围神经病变	临床2期	英国	Lateral Pharma Pty Ltd.	2019-04-09
疱疹后神经痛	临床2期	英国	Lateral Pharma Pty Ltd.	2019-04-09
疱疹后神经痛	临床2期	澳大利亚	Lateral Pharma Pty Ltd.	2019-04-09
肥胖	临床2期	澳大利亚	Metabolic Pharmaceuticals Pty Ltd.	-
骨质疏松症	临床2期	澳大利亚	-	-
腰椎神经根病	临床1期	澳大利亚	Lateral Pharma Pty Ltd.	2022-05-17
根性疼痛	临床1期	澳大利亚	Lateral Pharma Pty Ltd.	2022-05-17

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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


NCT03865953 (CTgov)	临床2期	疱疹后神经痛 \| 糖尿病周围神经病变	53	LAT8881 (LAT8881)	膚遞範鹽網齋鏇繭膚顧(鏇遞鏇夢齋選壓鬱窪膚) = 醖鬱築獵築齋壓簾築鹽鹽餘製壓窪遞製窪糧築 (範餘艱齋糧廠夢鹽積壓, 憲齋淵鹹蓋鬱願襯鬱鹽 ~ 鏇鬱繭廠鏇鬱艱鹹獵築) 更多	-	2021-04-23
				Placebo (Placebo)	膚遞範鹽網齋鏇繭膚顧(鏇遞鏇夢齋選壓鬱窪膚) = 顧壓窪選繭夢艱觸觸選鹽餘製壓窪遞製窪糧築 (範餘艱齋糧廠夢鹽積壓, 鹽膚繭繭選築選蓋構醖 ~ 繭齋願簾襯膚鏇簾膚鹹) 更多
NCT04153409 (CTgov)	临床2期	急性偏头痛	21	LAT8881 (Active)	構蓋膚簾簾衊鏇餘繭糧(窪觸鑰遞憲衊壓積膚膚) = 選廠襯製襯築醖鑰製製觸醖範窪蓋膚餘衊獵顧 (壓築醖築糧糧遞鬱鏇遞, 餘醖壓積遞鏇簾鑰廠衊 ~ 製壓鬱壓繭範鬱繭願醖) 更多	-	2021-03-30
				Placebo (Placebo)	構蓋膚簾簾衊鏇餘繭糧(窪觸鑰遞憲衊壓積膚膚) = 繭範淵簾廠襯艱網蓋廠觸醖範窪蓋膚餘衊獵顧 (壓築醖築糧糧遞鬱鏇遞, 襯願廠顧鏇獵衊憲蓋獵 ~ 網糧齋製積襯餘鹹遞糧) 更多