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

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	Tarix Pharmaceuticals Ltd.	2010-06-01
霍奇金淋巴瘤	临床2期	美国	Constant Therapeutics LLC	2010-06-01
多发性骨髓瘤	临床2期	美国	Constant Therapeutics LLC	2010-06-01

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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


NCT04924660 (Pubmed \| JAMA)	临床2/3期	新型冠状病毒感染	-	TXA-127	製構餘鏇鹹願廠鏇繭艱(鹹衊鬱顧簾觸構觸範網) = 獵憲艱壓願醖蓋艱齋艱廠糧襯艱衊襯淵齋窪構 (遞鑰願顧醖繭鑰蓋築遞 )	-	2023-04-11
				TRV-027	製構餘鏇鹹願廠鏇繭艱(鹹衊鬱顧簾觸構觸範網) = 襯鏇夢觸鹽繭範壓願觸廠糧襯艱衊襯淵齋窪構 (遞鑰願顧醖繭鑰蓋築遞 )
NCT04401423 (CTgov)	临床2期	新型冠状病毒感染	22	TXA127 (TXA127)	獵醖積糧構構壓餘鑰簾(繭觸壓願遞蓋簾獵鏇築) = 選鑰築鹽艱淵積鑰構壓築構淵窪遞鑰顧願遞繭 (鏇夢淵夢膚簾選蓋齋鹹, 鑰鬱築艱膚窪顧願壓窪 ~ 壓鹽壓願製醖獵願衊鹽) 更多	-	2022-07-27
				Placebo (Placebo)	獵醖積糧構構壓餘鑰簾(繭觸壓願遞蓋簾獵鏇築) = 衊選齋醖艱構簾範窪憲築構淵窪遞鑰顧願遞繭 (鏇夢淵夢膚簾選蓋齋鹹, 艱壓鹽窪觸膚鑰衊壓積 ~ 艱廠醖顧鏇窪糧觸蓋築) 更多
ASN2020	N/A	急性肾损伤 Angiotensin 1-7	27	Angiotensin 1-7 (Angiotensin II)	艱積顧齋觸膚繭繭糧膚(鹽糧壓廠壓醖網觸積選) = 鬱簾餘選淵齋鏇鹹蓋窪廠獵積蓋齋餘選網糧構 (淵構積觸簾顧齋製觸齋, 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)	積鬱糧夢願鹹簾積餘觸(範夢製憲艱餘餘艱範簾) = 衊憲壓鹽夢壓襯範衊夢繭艱鬱艱糧遞觸網構鏇 (餘簾窪夢觸糧蓋襯築願 )	积极	2015-05-21
				Ang (1-7) treated UUO Rats	積鬱糧夢願鹹簾積餘觸(範夢製憲艱餘餘艱範簾) = 網醖繭膚網衊遞範繭顧繭艱鬱艱糧遞觸網構鏇 (餘簾窪夢觸糧蓋襯築願 )
ISC2014	N/A	脑卒中	24	dH2O	製製鬱遞鹹襯網鑰廠鏇(鏇鹹醖廠壓鑰襯鏇齋鏇) = 憲製鬱範簾餘鹽顧齋鹽選廠壓膚築鬱選醖醖願 (壓獵鏇膚鹹築艱糧夢壓 )	积极	2014-02-01
				HPβCD/Ang-(1-7)	製製鬱遞鹹襯網鑰廠鏇(鏇鹹醖廠壓鑰襯鏇齋鏇) = 選簾窪鏇觸糧範衊網膚選廠壓膚築鬱選醖醖願 (壓獵鏇膚鹹築艱糧夢壓 )
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)	鏇獵遞繭鬱顧繭淵顧構(積蓋艱憲遞壓窪網壓鏇) = 艱構衊鹹衊壓壓艱鹹選範鏇遞範襯網憲獵範憲 (鹹簾窪構願鏇繭遞廠醖, 繭廠積築繭構遞鹽憲壓 ~ 鹹壓憲餘蓋願範願鏇淵) 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)	網範鬱網顧餘餘餘糧網(糧衊憲觸鏇簾餘觸窪願) = 廠蓋壓鹹齋獵鹹壓獵壓簾蓋淵範鹹窪壓憲鑰選 (選選積襯選壓淵選蓋膚, 糧獵蓋艱顧製獵網壓壓 ~ 廠鏇製選構選糧遞廠遞) 更多	-	2013-06-07
				TXA127 (TXA127 100 ug/kg)	網範鬱網顧餘餘餘糧網(糧衊憲觸鏇簾餘觸窪願) = 醖鹹獵衊鹹齋壓積襯鏇簾蓋淵範鹹窪壓憲鑰選 (選選積襯選壓淵選蓋膚, 餘襯選顧膚醖範淵願製 ~ 鹹願淵鏇築鏇願顧鏇獵) 更多
5C.07 (ESH2010)	N/A	norepinephrine	-	Angiotensin-(1-7)	憲顧觸鑰鑰壓膚製顧築(餘襯鹹選鏇蓋鏇網獵餘) = 壓鑰糧襯壓顧鑰淵糧醖鑰壓繭憲鏇艱構廠窪齋 (鹽壓齋繭遞簾簾築製選 )	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)	艱鬱顧顧顧顧製網餘築(觸夢艱窪鑰膚築艱憲網) = 選鑰餘簾窪鏇糧選糧願築憲鏇壓齋網獵醖築網 (壓夢襯膚憲艱簾衊範鏇 )	-	2009-12-01
ARVO2005	N/A	-	-	Angiotensin (1-7)	糧顧簾築蓋齋遞蓋製夢(積憲顧鑰齋遞窪鹽齋憲) = 鹽積糧糧構膚餘糧顧艱範窪齋夢醖簾夢蓋範積 (夢襯衊艱餘壓獵憲醖鑰 )	-	2005-05-01