Talfirastide(Talfirastide) - 药物靶点：Mas receptor_在研适应症：缺血性卒中，DMD相关的扩张型心肌病，杜氏肌营养不良症_专利_临床

概要

基本信息

药物类型

合成多肽

别名

Angiontensin(1-7)、Angiotensin (1-7)、Angiotensin I (1-7)

+ [4]

靶点

Mas receptor

作用机制

Mas receptor激动剂(原癌基因 Mas激动剂)

治疗领域

神经系统疾病心血管疾病遗传病与畸形+ [4]

在研适应症

缺血性卒中DMD相关的扩张型心肌病杜氏肌营养不良症+ [6]

非在研适应症

急性白血病急性淋巴细胞白血病急性髓性白血病+ [14]

原研机构

Tarix Orphan LLC

在研机构

Constant Therapeutics LLC

US Biotest, Inc.

Tarix Orphan LLC

非在研机构

Tarix Pharmaceuticals Ltd.

最高研发阶段临床2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C41H62N12O11

InChIKeyPVHLMTREZMEJCG-GDTLVBQBSA-N

CAS号51833-78-4

关联

25

项与 Talfirastide 相关的临床试验

NCT06482853

/ Recruiting早期临床1期IIT

Cardiovascular Effects of Angiotensin-(1-7) in Obesity Hypertension

Obesity is a global health concern that is associated with high blood pressure and an increased risk for developing cardiovascular disease. The purpose of this study is to find out if the investigational drug angiotensin-(1-7) can improve cardiovascular health in people with obesity and high blood pressure.

开始日期2024-12-01

申办/合作机构

Hershey Medical Center

[+1]

NCT06282965

/ Recruiting临床1/2期IIT

A Randomized, Double-blind, Placebo Controlled Study of the Safety and Efficacy of Angiotensin (1-7) in Persons With Moderate to Severe Traumatic Brain Injury (TBI)

The goal of this clinical trial is to test the safety of the drug Angiotensin (1-7) and learn whether it works well as a treatment in people who have suffered a moderate to severe traumatic brain injury (TBI).
The main questions this trial aims to answer are:
* Is Angiotensin (1-7) safe?
* Does Angiotensin (1-7) improve mental functioning and reduce physical signs of brain damage in people who have suffered a moderate to severe TBI?
Participants will:
* Complete 21 days of study treatment consisting of a once-daily injection.
* Provide blood samples.
* Undergo two magnetic resonance imaging (MRI) scans of the brain.
* Complete specific tasks and questionnaires that allow researchers to evaluate the participant's brain and psychological functioning.
Researchers will compare three groups: two groups that receive different doses of Angiotensin (1-7) and one group that receives a look-alike treatment with no active drug. This will allow researchers to see if the drug has any negative effects and whether it improves mental functioning and physical signs of brain damage after a TBI.

开始日期2024-05-28

申办/合作机构

University of Arizona

RBR-3bhkdg2

/ RecruitingN/A

Angiotensin formulations-(1-7) its actions on physical performance and injury repair muscular

开始日期2024-03-28

申办/合作机构

Universidade Federal de Ouro Preto

100 项与 Talfirastide 相关的临床结果

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100 项与 Talfirastide 相关的转化医学

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100 项与 Talfirastide 相关的专利（医药）

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638

项与 Talfirastide 相关的文献（医药）

2024-12-05·ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Intranasal liposomal angiotensin-(1-7) administration reduces inflammation and viral load in the lungs during SARS-CoV-2 infection in K18-hACE2 transgenic mice

Article

作者: Frézard, Frédéric ; Guimarães, Pedro Pires Goulart ; Guimarães, Lays Cordeiro ; Costa, Pedro Augusto Carvalho ; dos Santos, Robson Augusto Souza ; Fernandez, Clara Couto ; Teixeira, Mauro Martins ; Figueiredo, Maria Marta ; Mendes, Sabrina

ABSTRACT:

To effectively reduce the health impact of coronavirus disease (COVID-19), it is essential to adopt comprehensive strategies to protect individuals from severe acute respiratory syndrome. In that sense, much effort has been devoted to the discovery and repurposing of effective antiviral and anti-inflammatory molecules. The endogenous peptide angiotensin-(1-7) [Ang-(1-7)] has been recently proposed as a promising anti-inflammatory agent to control respiratory infections. Liposomes also emerged as a safe and effective drug carrier system for local drug delivery to the lungs. In this context, the aim of this study was to develop a liposomal formulation of Ang-(1-7) [LAng (1-7)] and investigate its impact on animal survival as well as its antiviral and anti-inflammatory efficacies after intranasal administration in transgenic K18-hACE2 mice infected with SARS-CoV-2. The liposomal formulation was prepared by the ethanol injection method, exhibiting a mean diameter of 100 nm and a polydispersity index of 0.1. Following treatment of infected mice every 12 hours for 5 days, LAng (1-7) extended animal survival compared to the control groups that received either empty liposomes, free Ang-(1-7), or phosphate-buffered saline. Furthermore, the treatment with LAng (1-7) significantly decreased the viral load, as well as IL-6 and tumor necrosis factor levels in the lungs. Conventional treatment with remdesivir by parenteral route used as a positive control promoted similar effects, leading to improved survival rates and reduced viral load in the lungs without significant effects on IL-6 level. In conclusion, liposomal Ang-(1-7) emerges as a promising formulation to improve the treatment and decrease the severity of respiratory infections, such as COVID-19.

2024-11-01·INFLAMMATION RESEARCH

Angiotensin-(1–7) decreases inflammation and lung damage caused by betacoronavirus infection in mice

Article

作者: Queiroz-Junior, Celso M ; Oliveira, Leonardo C ; Carvalho, Antônio Felipe S ; Santos, Felipe Rocha da Silva ; Carneiro, Fernanda S ; Resende, Filipe ; Lara, Edvaldo S ; Santos, Robson A S ; Cardoso, Camila ; Souza-Costa, Luiz Pedro ; Teixeira, Mauro M ; Zaidan, Isabella ; Monteiro, Adelson Héric A ; Tavares, Luciana P ; Sousa, Lirlândia P ; Costa, Vivian V ; Lima, Erick Bryan de Sousa ; Russo, Remo C ; Chaves, Ian de Meira

OBJECTIVE:

Pro-resolving molecules, including the peptide Angiotensin-(1-7) [Ang-(1-7)], have potential adjunctive therapy for infections. Here we evaluate the actions of Ang-(1-7) in betacoronavirus infection in mice.

METHODS:

C57BL/6J mice were infected intranasally with the murine betacoronavirus MHV-3 and K18-hACE2 mice were infected with SARS-CoV-2. Mice were treated with Ang-(1-7) (30 µg/mouse, i.p.) at 24-, 36-, and 48-hours post-infection (hpi) or at 24, 36, 48, 72, and 96 h. For lethality evaluation, one additional dose of Ang-(1-7) was given at 120 hpi. At 3- and 5-days post- infection (dpi) blood cells, inflammatory mediators, viral loads, and lung histopathology were evaluated.

RESULTS:

Ang-(1-7) rescued lymphopenia in MHV-infected mice, and decreased airways leukocyte infiltration and lung damage at 3- and 5-dpi. The levels of pro-inflammatory cytokines and virus titers in lung and plasma were decreased by Ang-(1-7) during MHV infection. Ang-(1-7) improved lung function and increased survival rates in MHV-infected mice. Notably, Ang-(1-7) treatment during SARS-CoV-2 infection restored blood lymphocytes to baseline, decreased weight loss, virus titters and levels of inflammatory cytokines, resulting in improvement of pulmonary damage, clinical scores and lethality rates.

CONCLUSION:

Ang-(1-7) protected mice from lung damage and death during betacoronavirus infections by modulating inflammation, hematological parameters and enhancing viral clearance.

2024-11-01·EXPERIMENTAL NEUROLOGY

The angiotensin (1–7) glycopeptide PNA5 improves cognition in a chronic progressive mouse model of Parkinson's disease through modulation of neuroinflammation

Article

作者: Doyle, Kristian P ; Madhavan, Lalitha ; Polt, Robin ; Bernard, Kelsey ; Mota, Jesus A ; Hay, Meredith ; Wene, Paige ; Corenblum, Mandi J ; Saez, Juben L ; Falk, Torsten ; Heien, M Leandro ; Bartlett, Mitchell J

Cognitive decline in Parkinson's Disease (PD) is a prevalent and undertreated aspect of disease. Currently, no therapeutics adequately improve this aspect of disease. It has been previously shown that MAS receptor agonism via the glycosylated Angiotensin (1-7) peptide, PNA5, effectively reduces cognitive decline in models of vascular contributions to cognitive impairment and dementia (VCID). PNA5 has a brain/plasma ratio of 0.255 indicating good brain penetration. The goal of the present study was to determine if (1) systemic administration of PNA5 rescued cognitive decline in a mouse model of PD, and (2) if improvements in cognitive status could be correlated with changes to histopathological or blood plasma-based changes. Mice over-expressing human, wild-type α-synuclein (αSyn) under the Thy1 promoter (Thy1-αSyn mice, "line 61") were used as a model of PD with cognitive decline. Thy1-αSyn mice were treated with a systemic dose of PNA5, or saline (1 mg/kg/day) beginning at 4 months of age and underwent behavioral testing at 6 months, compared to WT. Subsequently, mice brains were analyzed for changes to brain pathology, and blood plasma was examined with a Multiplex Immunoassay for peripheral cytokine changes. Treatment with PNA5 reversed cognitive dysfunction measured by Novel Object Recognition and spontaneous alteration in a Y-maze in Thy1-αSyn mice. PNA5 treatment was specific to cognitive deficits, as fine-motor disturbances were unchanged. Enhanced cognition was associated with decreases in hippocampal inflammation and reductions in circulating levels of Macrophage Induced Protein (MIP-1β). Additionally, neuronal loss was blunted within the CA3 hippocampal region of PNA5-treated αsyn mice. These data reveal that PNA5 treatment reduces cognitive dysfunction in a mouse model of PD. These changes are associated with decreased MIP-1β levels in plasma identifying a candidate biomarker for target engagement. Thus, PNA5 treatment could potentially fill the therapeutic gap for cognitive decline in PD.

2

项与 Talfirastide 相关的新闻（医药）

2024-03-04

·PRNewswire

Constant Therapeutics Announces First Patient Dosed in Phase 2 Clinical Trial of TXA127 in Duchenne Muscular Dystrophy-Associated Cardiomyopathy

BOSTON, March 4, 2024 /PRNewswire/ -- Constant Therapeutics LLC, a biopharmaceutical company focused on the development of treatments impacting the Alternative Renin-Angiotensin System, today announced that the first patient was dosed March 3, 2024, in the Company's phase 2 clinical trial of TXA127, the Company's lead peptide product under development as a potential treatment for Duchenne Muscular Dystrophy-associated (DMD-associated) Cardiomyopathy. The phase 2 trial is an open-label, multi-center trial designed to evaluate the safety and efficacy in non-ambulatory patients with DMD-associated Cardiomyopathy who are 16 years and older and who are receiving systemic glucocorticoids. Patients will receive 6 months of treatment and have the option to enter a 12-month extension study. The study is being conducted in Israel at Sheba Medical Center and Hadassah Medical Center and is expected to enroll 10 patients. "This is a significant milestone for Constant and for the DMD community," said Rick Franklin, CEO of Constant Therapeutics. "There are few treatments for DMD patients with cardiomyopathy, and heart failure is a leading cause of death in this disease. We are excited to initiate this carefully designed trial, and we look forward to sharing the data with the DMD community upon completion of the trial." About Constant Therapeutics LLC Constant Therapeutics LLC is a private biopharmaceutical company focused on the development of treatments that effect the Alternative Renin-Angiotensin System. The lead compound, TXA127, is a pharmaceutical formulation of the naturally occurring peptide Angiotensin (1-7) and is being developed for the treatment of stroke recovery and DMD-associated Cardiomyopathy. For more information on Constant Therapeutics, please visit our website at . About TXA127 TXA127 is a pharmaceutical formulation of the naturally occurring human peptide angiotensin-(1‐7). In addition to its specific effects in cardiac dysfunction, TXA127 has shown therapeutic activity in animal models of chronic stroke, Duchenne Muscular Dystrophy (DMD), Limb‐Girdle Muscular Dystrophy (LGMD), Congenital Muscular Dystrophy (MDC1A), Marfan Syndrome and Epidermolysis Bullosa. Contact: [email protected] +1-617-245-0289 SOURCE Constant Therapeutics

临床2期

2024-01-09

·PRNewswire

Constant Therapeutics Announces First Patient Dosed in Phase 2 Clinical Trial of TXA127 in Ischemic Stroke Recovery

BOSTON, Jan. 9, 2024 /PRNewswire/ -- Constant Therapeutics LLC, a biopharmaceutical company focused on the development of treatments impacting the Alternative Renin-Angiotensin System, today announced that the first patient has been dosed in the Company's phase 2 clinical trial of TXA127, the Company's lead peptide product under development as a potential treatment for ischemic stroke recovery. The phase 2 trial is a randomized, placebo-controlled, double-blind, hybrid decentralized study designed to evaluate the safety and efficacy in ischemic stroke patients who are 18 to 85 years old and who are 6 to 24 months post stroke event. Patients will receive 3 months of treatment. The study is being conducted in Israel at Sheba Medical Center in collaboration with Sabar Health for the home visits, and it is expected to enroll 50 patients. "There are no drugs available to treat chronic stroke, but the design and logistics of clinical trials in these patients is particularly difficult. We are fortunate to have been able to put together the infrastructure needed, with the participation of Sabar Health and Sheba Medical Center. This unique combination will allow us to test TXA127 for this important unmet medical need," said Rick Franklin, CEO of Constant Therapeutics." About Constant Therapeutics LLC Constant Therapeutics LLC is a private biopharmaceutical company focused on the development of treatments that effect the Alternative Renin-Angiotensin System. The lead compound, TXA127, is a pharmaceutical formulation of the naturally occurring peptide Angiotensin (1-7) and is being developed for the treatment of stroke recovery and DMD-associated Cardiomyopathy. For more information on Constant Therapeutics, please visit our website at . About TXA127 TXA127 is a pharmaceutical formulation of the naturally occurring human peptide angiotensin-(1‐7). In addition to its specific effects in ischemic stroke, TXA127 has shown therapeutic activity in animal models Duchenne Muscular Dystrophy (DMD), Limb‐Girdle Muscular Dystrophy (LGMD), Congenital Muscular Dystrophy (MDC1A), Marfan Syndrome and Epidermolysis Bullosa. Contact: [email protected] +1-617-245-0289 SOURCE Constant Therapeutics

临床2期

100 项与 Talfirastide 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11720

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
缺血性卒中	临床2期	以色列	Constant Therapeutics LLC	2023-11-26
DMD相关的扩张型心肌病	临床2期	以色列	Constant Therapeutics LLC	2023-08-31
杜氏肌营养不良症	临床2期	以色列	Constant Therapeutics LLC	2023-08-31
新型冠状病毒感染	临床2期	美国	Constant Therapeutics LLC	2021-02-10
急性白血病	临床2期	美国	Tarix Pharmaceuticals Ltd.	2013-12-01
移植物抗宿主病	临床2期	美国	Tarix Pharmaceuticals Ltd.	2013-12-01
代谢性疾病	临床2期	美国	Tarix Pharmaceuticals Ltd.	2012-03-01
霍奇金淋巴瘤	临床2期	美国	Constant Therapeutics LLC	2010-06-01
霍奇金淋巴瘤	临床2期	美国	Tarix Pharmaceuticals Ltd.	2010-06-01
多发性骨髓瘤	临床2期	美国	Tarix Pharmaceuticals Ltd.	2010-06-01

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04924660 (Pubmed \| JAMA)	临床2/3期	新型冠状病毒感染	-	TXA-127	選壓遞繭淵艱膚蓋廠淵(繭顧簾艱鹽鏇遞憲壓鬱) = 醖膚夢鬱顧鹽製壓鹹鹹膚築顧齋築憲醖獵鹹繭 (構淵蓋衊鬱顧糧襯製網 )	-	2023-04-11
				TRV-027	選壓遞繭淵艱膚蓋廠淵(繭顧簾艱鹽鏇遞憲壓鬱) = 淵鏇壓襯簾淵鬱遞範觸膚築顧齋築憲醖獵鹹繭 (構淵蓋衊鬱顧糧襯製網 )
NCT04401423 (CTgov)	临床2期	新型冠状病毒感染	22	TXA127 (TXA127)	廠觸構艱齋齋鑰壓膚淵(築積窪選鹽遞窪醖構夢) = 築鹽鏇獵壓製鏇窪簾遞遞淵製衊膚鏇觸醖築築 (積餘餘艱遞觸築構艱築, 鏇製糧蓋願壓糧襯鹹顧 ~ 築範窪獵積繭獵顧膚鬱) 更多	-	2022-07-27
				Placebo (Placebo)	廠觸構艱齋齋鑰壓膚淵(築積窪選鹽遞窪醖構夢) = 淵糧糧積膚襯繭製觸淵遞淵製衊膚鏇觸醖築築 (積餘餘艱遞觸築構艱築, 夢製淵衊艱鬱積餘襯鹽 ~ 艱蓋艱餘鹽襯廠繭壓淵) 更多
ASN2020	N/A	急性肾损伤 Angiotensin 1-7	27	Angiotensin 1-7 (Angiotensin II)	築鑰鑰範艱鑰壓壓鏇簾(窪選鹽淵網網夢鬱繭選) = 製憲範鏇壓鹹淵窪糧鏇艱廠繭繭蓋選願鹽願壓 (鏇簾鏇構醖鏇願衊襯廠, 0.93 ~ 1.0)	积极	2020-10-19
FP180 (ERA2015)	N/A	肾脏疾病	-	ANGIOTENSIN (1-7) (Unilateral Ureteral Obstructed (UUO) Rats)	憲夢衊膚遞壓築餘選夢(顧獵淵製鏇鬱膚積鹽蓋) = 襯壓製鹹淵餘鏇鑰鏇鬱廠積顧廠選築遞築鹽艱 (鹽蓋選廠製蓋蓋夢鹽夢 )	积极	2015-05-21
				Ang (1-7) treated UUO Rats	憲夢衊膚遞壓築餘選夢(顧獵淵製鏇鬱膚積鹽蓋) = 醖淵鹽鬱築遞蓋艱觸網廠積顧廠選築遞築鹽艱 (鹽蓋選廠製蓋蓋夢鹽夢 )
ISC2014	N/A	脑卒中	24	dH2O	窪艱築鬱廠淵鏇餘遞鑰(選夢構膚鹽襯築觸蓋艱) = 壓餘選衊鹽廠鬱選膚廠齋鏇淵糧淵壓繭衊蓋夢 (廠構糧構襯鏇積餘鬱鏇 )	积极	2014-02-01
				HPβCD/Ang-(1-7)	窪艱築鬱廠淵鏇餘遞鑰(選夢構膚鹽襯築觸蓋艱) = 蓋憲餘廠遞醖憲糧餘繭齋鏇淵糧淵壓繭衊蓋夢 (廠構糧構襯鏇積餘鬱鏇 )
NCT01553539 (CTgov)	临床2期	骨癌 \| 软骨肉瘤 \| 复发性骨肉瘤 ... 更多	20	laboratory biomarker analysis+therapeutic angiotensin-(1-7)	鬱觸廠積選積製築夢夢(壓積鏇願鬱願壓構壓壓) = 鹹膚鏇壓憲糧艱選鏇窪艱鹹鏇遞鹹鬱製遞襯夢 (廠壓構衊製獵製網廠簾, 廠餘淵窪廠淵蓋廠憲範 ~ 觸簾製餘積鑰夢鹹糧衊) 更多	-	2014-01-30
NCT00771810 (CTgov)	临床2期	贫血 \| 血小板减少症 \| 中性粒细胞减少 ... 更多	34	Placebo (Placebo)	鹽醖網願築選廠簾衊遞(鹽製簾構簾餘遞艱願鹹) = 網選製淵顧鏇夢窪壓蓋鬱遞範醖醖鹹網遞夢製 (獵鹽鹹觸襯顧齋顧觸膚, 鏇糧積構選糧遞齋簾壓 ~ 鏇願觸憲淵蓋鬱壓鏇遞) 更多	-	2013-06-07
				TXA127 (TXA127 100 ug/kg)	鹽醖網願築選廠簾衊遞(鹽製簾構簾餘遞艱願鹹) = 艱鹹襯獵繭蓋蓋糧鑰製鬱遞範醖醖鹹網遞夢製 (獵鹽鹹觸襯顧齋顧觸膚, 製餘膚積觸鹹鑰簾衊糧 ~ 繭窪範餘鑰衊積簾齋製) 更多
5C.07 (ESH2010)	N/A	norepinephrine	-	Angiotensin-(1-7)	衊糧夢餘膚憲壓鹹夢蓋(鑰鏇夢遞憲網獵觸範齋) = 憲齋鹹齋艱鏇蓋簾淵憲鏇襯鏇壓鹽膚艱襯鹹願 (艱願範憲糧築夢淵積艱 )	积极	2010-06-01
NCT00471562 (Pubmed \| Clin Cancer Res)	临床1期	转移性实体瘤 \| 晚期恶性实体瘤	18	Angiotensin-(1-7)	顧蓋廠鹽艱醖蓋膚齋鹽(餘齋蓋窪構齋築衊鬱醖) = 窪糧築範淵選獵積築壓簾艱廠淵遞製壓淵鹹選 (壓艱願觸製鏇繭鑰遞艱 )	-	2009-12-01
ARVO2005	N/A	-	-	Angiotensin (1-7)	廠醖簾獵醖製糧淵壓蓋(艱築簾鏇膚糧選餘鹹積) = 膚鏇艱製衊鏇鬱鑰遞餘網構艱憲構願積餘糧襯 (膚衊夢齋窪窪餘醖願製 )	-	2005-05-01