R2R01(R2R01) - 药物靶点：RXFP1_在研适应症：心脏衰竭，急性肾损伤，肝肾综合征_专利_临床

概要

基本信息

药物类型

合成多肽

别名-

靶点

RXFP1

作用方式

激动剂

作用机制

RXFP1激动剂(松弛素受体-1激动剂)

治疗领域

心血管疾病消化系统疾病泌尿生殖系统疾病

在研适应症

心脏衰竭急性肾损伤肝肾综合征+ [2]

非在研适应症-

原研机构

River 2 Renal Corp.

在研机构

River 2 Renal Corp.

Sanofi

非在研机构-

权益机构-

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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关联

3

项与 R2R01 相关的临床试验

NCT06264310

/ Completed临床2期

A Phase 2, Double-Blind, Placebo-Controlled, Dose Range Finding Study to Assess Safety, Tolerability, Efficacy and Pharmacokinetics of the Relaxin Agonist R2R01 Combined With Standard of Care Versus Standard of Care Alone in Outpatients With Worsening Heart Failure (WHF)

This Study Aims to Evaluate the Safety, Tolerability and Efficacy of R2R01 Combined With SOC as Compared to SOC Alone in Outpatients With Worsening Heart Failure (WHF)

开始日期2024-03-01

申办/合作机构

River 2 Renal Corp.

[+1]

NCT05875948

/ Recruiting临床2期

A Single-blind, Phase 2, Multi-center, Randomized Study to Assess Safety, Tolerability, Efficacy and Pharmacokinetics of the R2R01 Plus Terlipressin Versus Terlipressin Alone in Patients With Hepatorenal Syndrome - Acute Kidney Injury

This study aims to evaluate the safety, tolerability and efficacy of R2R01 combined with terlipressin as compared to terlipressin alone in the treatment of patients with HRS-AKI

开始日期2023-06-30

申办/合作机构

River 2 Renal Corp.

NL-OMON51081

/ CompletedN/A

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Ranging Study in Healthy Volunteers to Assess Safety, Tolerability, and Evaluate the Pharmacokinetics and Pharmacodynamics of R2R01 - Placebo-controlled SAD/MAD of R2R01

开始日期2021-04-30

申办/合作机构

River 2 Renal Corp.

100 项与 R2R01 相关的临床结果

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100 项与 R2R01 相关的转化医学

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100 项与 R2R01 相关的专利（医药）

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2

项与 R2R01 相关的文献（医药）

2025-02-13·Journal of Medicinal Chemistry

Optimization of Single Relaxin B-Chain Peptide Leads to the Identification of R2R01, a Potent, Long-Acting RXFP1 Agonist for Cardiovascular and Renal Diseases

Article

作者: Di Marco, Annalise ; Corbier, Alain ; Veneziano, Maria ; Monteagudo, Edith ; Maillère, Bernard ; Roversi, Daniela ; Tucci, Federica ; Duclos, Olivier ; Gervat, Vincent ; Santoprete, Alessia ; Gauzy-Lazo, Laurence ; Illiano, Stephane ; Azam, Aurélien ; Magotti, Paola ; Orsatti, Laura ; Ingenito, Raffaele ; Mallart, Sergio ; Chénedé, Xavier ; Esposito, Simone ; Pasquier, Olivier ; Janiak, Philip ; Minoletti, Claire ; Bianchi, Elisabetta ; Marguet, Frank ; Caretti, Fulvia ; Brasseur, Denis ; Poirier, Bruno ; Bresciani, Alberto

Peptide 1, a C18 fatty acid-modified single-chain relaxin analogue, was recently identified as a potent, selective, and long-lasting relaxin family peptide receptor 1 (RXFP1) agonist. Further advanced pharmacokinetic profiling of this compound highlighted elevated levels of oxidative metabolism occurring in dogs and mini pigs but only marginally in rats. This study aimed to design long-lasting relaxin analogues with increased stability against metabolic oxidation while securing subnanomolar RXFP1 potency. Key structural elements, including fatty acid chain length, attachment position, and linker structure, were modified to reduce oxidative metabolism and improve pharmacokinetic parameters. Additionally, incorporating α-methyl lysine (Mly) at position 30, alongside other selective sequence mutations, resulted in several analogues with subnanomolar RXFP1 potency and improved duration of action compared to 1. Compound 21 (R2R01) was then selected as a candidate for an in-depth characterization. It is currently undergoing phase 2 clinical development for renal and cardiovascular diseases.

2024-07-01·British Journal of Pharmacology

R2R01: A long‐acting single‐chain peptide agonist of RXFP1 for renal and cardiovascular diseases

Article

作者: Mallart, Sergio ; Janiak, Philip ; Maillere, Bernard ; Philippo, Christophe ; Prigent, Philippe ; Corbier, Alain ; Azam, Aurélien ; Illiano, Stephane ; Poirier, Bruno ; Ingenito, Raffaele ; Gillot, Florence ; Gauzy-Lazo, Laurence ; Chenede, Xavier ; Duclos, Olivier ; Riva, Laurence ; Guillotel, Michel ; Bianchi, Elisabetta ; Bernard, Carine ; Pasquier, Olivier ; Briand, Veronique

AbstractBackgroundThe therapeutic potential of relaxin for heart failure and renal disease in clinical trials is hampered by the short half‐life of serelaxin. Optimization of fatty acid‐acetylated single‐chain peptide analogues of relaxin culminated in the design and synthesis of R2R01, a potent and selective RXFP1 agonist with subcutaneous bioavailability and extended half‐life.Experimental ApproachCellular assays and pharmacological models of RXFP1 activation were used to validate the potency and selectivity of R2R01. Increased renal blood flow was used as a translational marker of R2R01 activity. Human mastocytes (LAD2 cells) were used to study potential pseudo‐allergic reactions and CD4+ T‐cells to study immunogenicity. The pharmacokinetics of R2R01 were characterized in rats and minipigs.Key ResultsIn vitro, R2R01 had comparable potency and efficacy to relaxin as an agonist for human RXFP1. In vivo, subcutaneous administration of R2R01 increased heart rate and renal blood flow in normotensive and hypertensive rat and did not show evidence of tachyphylaxis. R2R01 also increased nipple length in rats, used as a chronic model of RXFP1 engagement. Pharmacokinetic studies showed that R2R01 has a significantly extended terminal half‐life. The in vitro assays with LAD2 cells and CD4+ T‐cells showed that R2R01 had low potential for pseudo‐allergic and immunogenic reactions, respectively.Conclusion and implicationsR2R01 is a potent RXFP1 agonist with an extended half‐life that increases renal blood flow in various settings including normotensive and hypertensive conditions. The preclinical efficacy and safety data supported clinical development of R2R01 as a potential new therapy for renal and cardiovascular diseases.

100 项与 R2R01 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
心脏衰竭	临床2期	意大利	River 2 Renal Corp.	2024-03-01
心脏衰竭	临床2期	美国	River 2 Renal Corp.	2024-03-01
心脏衰竭	临床2期	德国	River 2 Renal Corp.	2024-03-01
急性肾损伤	临床2期	美国	River 2 Renal Corp.	2023-06-30
肝肾综合征	临床2期	美国	River 2 Renal Corp.	2023-06-30
心血管疾病	临床前	法国	Sanofi	2024-03-07
肾脏疾病	临床前	法国	Sanofi	2024-03-07