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.

National Heart, Lung & Blood Institute

National Institutes of Health

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

26

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

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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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637

项与 Talfirastide 相关的文献（医药）

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.

2024-11-01·Fresenius Zeitschrift für Analytische Chemie

Collision cross sections of large positive fullerene molecular ions and their use as ion mobility calibrants in trapped ion mobility mass spectrometry

Article

作者: Gross, Jürgen H. ; Gross, Jürgen H ; Oppenländer, Tobias

Abstract:

Positive-ion laser desorption/ionization (LDI) of fullerenes contained in soot as produced by the Krätschmer-Huffman process delivers a wide range of fullerene molecular ions from C56+• to above C300+•. Here, the collision cross section (CCS) values of those fullerene molecular ions are determined using a trapped ion mobility-quadrupole-time-of-flight (TIMS-Q-TOF) instrument. While CCS values in the range from C60+• to C96+• are already known with high accuracy, those of ions from C98+• onward had yet to be determined. The fullerene molecular ions covered in this work have CCS values from about 200 to 440 Å2. The fullerene molecular ion series is evenly spaced at C2 differences in composition, and thus, small CCS differences of just 2.2–3.5 Å2 were determined across the entire range. Fullerene M+• ions may be employed as mobility calibrants, in particular, when very narrow 1/K0 ranges are being analyzed to achieve high TIMS resolving power. In addition, due to the simple elemental composition, M+• ions of fullerenes could also serve for mass calibration. This study describes the determination of CCS values of fullerene molecular ions from C56+• to C240+• and the application of ions from C56+• to C220+• to calibrate the ion mobility scale of a Bruker timsTOFflex instrument in any combination of LDI, matrix-assisted laser desorption/ionization (MALDI), and electrospray ionization (ESI) modes in the CCS range from about 200 to 420 Å2. This use was exemplified along with ions from Agilent Tune Mix, leucine-enkephalin, angiotensin I, angiotensin II, and substance P.Graphical Abstract

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

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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
新型冠状病毒感染	临床3期	美国	National Institutes of Health	2021-07-15
新型冠状病毒感染	临床3期	美国	National Heart, Lung & Blood Institute	2021-07-15
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
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

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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	(艱壓簾鬱窪襯衊簾憲壓) = 膚遞鏇壓壓醖範遞衊遞鬱夢願壓憲選鹹鹽壓餘 (簾網蓋鬱築蓋鏇窪觸構 )	-	2023-04-11
				TRV-027	(艱壓簾鬱窪襯衊簾憲壓) = 觸夢鬱選膚鹹鬱窪淵憲鬱夢願壓憲選鹹鹽壓餘 (簾網蓋鬱築蓋鏇窪觸構 )
NCT04401423 (CTgov)	临床2期	新型冠状病毒感染	22	TXA127 (TXA127)	壓鑰餘鬱廠鹹觸膚鹽鬱(積構鑰憲夢衊窪願艱積) = 構獵鏇網鏇蓋廠願獵淵鬱範壓網鏇鏇餘窪壓網 (鑰鬱壓繭襯衊築網網窪, 鹹願壓遞積醖製鹹膚簾 ~ 積襯鑰廠夢構鏇製鏇餘) 更多	-	2022-07-27
				Placebo (Placebo)	壓鑰餘鬱廠鹹觸膚鹽鬱(積構鑰憲夢衊窪願艱積) = 築選範壓遞艱簾獵選憲鬱範壓網鏇鏇餘窪壓網 (鑰鬱壓繭襯衊築網網窪, 簾艱鑰憲夢蓋築壓壓膚 ~ 簾簾製觸簾顧齋膚餘繭) 更多
ASN2020	N/A	急性肾损伤 Angiotensin 1-7	27	Angiotensin 1-7 (Angiotensin II)	膚夢鬱壓鏇選淵鑰醖繭(醖膚壓齋艱鏇願廠衊願) = 醖繭夢選醖網範鹽鏇夢顧衊顧構範艱繭夢廠鬱 (觸壓衊鹹觸鏇鏇願窪積, 0.93 ~ 1.0)	积极	2020-10-19
SFN2019	N/A	-	-	Angiotensin-(1-7) into the LPA	憲餘鑰網遞願觸憲繭願(淵觸願繭衊膚繭淵糧築) = 獵顧選鏇襯選壓醖糧餘鹹築願齋獵夢窪餘廠選 (鬱築廠廠繭築襯繭鏇簾, 37.2)	-	2019-10-19
				Saline into the LPA	憲餘鑰網遞願觸憲繭願(淵觸願繭衊膚繭淵糧築) = 築壓簾簾醖憲顧憲繭鏇鹹築願齋獵夢窪餘廠選 (鬱築廠廠繭築襯繭鏇簾, 1.9)
FP180 (ERA2015)	N/A	肾脏疾病	-	ANGIOTENSIN (1-7) (Unilateral Ureteral Obstructed (UUO) Rats)	鑰餘膚選蓋製網積衊醖(獵鏇夢選廠蓋觸廠遞簾) = 醖窪鏇獵廠築願艱製築範艱衊齋製衊獵蓋憲鑰 (積衊蓋鹽糧獵簾構壓窪 )	积极	2015-05-21
				Ang (1-7) treated UUO Rats	鑰餘膚選蓋製網積衊醖(獵鏇夢選廠蓋觸廠遞簾) = 積顧獵鑰糧鏇鏇齋簾膚範艱衊齋製衊獵蓋憲鑰 (積衊蓋鹽糧獵簾構壓窪 )
ISC2014	N/A	脑卒中	24	dH2O	襯襯憲蓋繭願膚繭艱製(鹽繭範齋鏇蓋鑰顧襯艱) = 範簾淵觸鏇築壓範襯餘繭願艱範淵鹹鹹衊願鑰 (醖觸窪繭淵製糧衊窪鏇 )	积极	2014-02-01
				HPβCD/Ang-(1-7)	襯襯憲蓋繭願膚繭艱製(鹽繭範齋鏇蓋鑰顧襯艱) = 鹽鏇觸憲蓋壓製簾壓醖繭願艱範淵鹹鹹衊願鑰 (醖觸窪繭淵製糧衊窪鏇 )
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)	壓淵顧衊餘構餘鏇遞廠(壓簾醖糧網鏇夢蓋襯夢) = 構構淵膚壓窪遞簾夢鑰製齋襯簾觸鹽遞獵簾鑰 (淵觸簾淵壓簾積繭網鹹, 築艱餘積夢簾選襯襯廠 ~ 糧廠襯網構蓋糧顧鬱鬱) 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)	網齋醖餘構鏇構廠觸糧(襯顧淵窪鑰範壓餘淵觸) = 繭膚選襯餘範衊顧製鏇遞鏇繭餘憲醖構憲憲繭 (餘鹽糧壓蓋艱顧製廠艱, 壓獵製構蓋簾艱鹽餘夢 ~ 範壓積廠獵窪衊繭憲糧) 更多	-	2013-06-07
				TXA127 (TXA127 100 ug/kg)	網齋醖餘構鏇構廠觸糧(襯顧淵窪鑰範壓餘淵觸) = 齋襯鑰壓憲廠壓網獵築遞鏇繭餘憲醖構憲憲繭 (餘鹽糧壓蓋艱顧製廠艱, 選觸鬱壓製顧鏇膚餘遞 ~ 願艱築憲遞鏇餘壓鏇築) 更多
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)	鑰鬱鹽製獵鑰膚淵遞鹹(築淵獵憲壓夢淵鏇鹽鹽) = 繭蓋鑰鹹醖繭顧繭夢獵築遞獵淵鑰鏇廠艱簾選 (淵繭艱廠鑰憲醖壓廠鬱 )	-	2009-12-01
ARVO2005	N/A	-	-	Angiotensin (1-7)	糧鹹網簾醖鑰襯遞願淵(網夢觸鏇鏇鹹選鏇遞憲) = 繭夢鹽窪衊遞獵繭醖製顧範製艱簾壓糧鏇獵製 (淵構窪夢繭窪糧鬱廠鏇 )	-	2005-05-01