Delving into the Latest Updates on Madeleine Pharmaceuticals Pty Ltd. with Synapse

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1

项与 Madeleine Pharmaceuticals Pty Ltd. 相关的药物

Atrial natriuretic factor prohormone 31-67(Madeleine Pharmaceuticals)

靶点

NPR

作用机制

NPR激动剂

在研机构

Medtronic Plc

原研机构

Madeleine Pharmaceuticals Pty Ltd.

在研适应症

心脏衰竭

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期-

3

项与 Madeleine Pharmaceuticals Pty Ltd. 相关的临床试验

ACTRN12612000576820 / Completed临床1期

The pharmacokinetics, tolerability and safety of vessel dilator (VSDL) peptide following subcutaneous infusion to steady state in patients with stable congestive heart failure and moderate renal impairment.

开始日期2012-03-08

申办/合作机构

Madeleine Pharmaceuticals Pty Ltd.

ACTRN12611000806965 / Completed临床1期

The pharmacokinetics and pharmacodynamics of subcutaneously administered vessel dilator peptide in stable patients with chronic heart failure and moderate renal impairment.

开始日期2011-12-01

申办/合作机构

Madeleine Pharmaceuticals Pty Ltd.

ACTRN12609000998246 / Completed临床1期

An Exploratory, Single Centre, Open Label, single and Multidose, Safety and Efficacy Study of the Treatment of Acute Decompensated Congestive Heart Failure with Vessel Dilator Peptide by Intravenous Infusion.

开始日期2010-08-27

申办/合作机构

Madeleine Pharmaceuticals Pty Ltd.

100 项与 Madeleine Pharmaceuticals Pty Ltd. 相关的临床结果

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0 项与 Madeleine Pharmaceuticals Pty Ltd. 相关的专利（医药）

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1

项与 Madeleine Pharmaceuticals Pty Ltd. 相关的文献（医药）

2017-09-01·Hypertension

Abstract 027: ProANP 31-67 and Renal Function in Heart Failure

作者: Schiermeyer, Katie ; Xu, Peng ; Gildea, John J ; Felder, Robin ; Mahan, Larry ; Geimer, T R

The physiologic interplay between heart and kidney is best understood in the context of heart failure (HF). Two-thirds of HF patients suffer from cardiorenal syndrome (CRS) - heart failure with renal insufficiency wherein both organs contribute to their reciprocal decline. Four peptides are released from an atrial natriuretic prohormone in response to atrial-ventricular wall stress in HF. One in particular, a well characterized 28 a.a cyclic peptide from the C-terminus termed ANP elicits systemic vasodilation via cGMP release and was developed as Natrecor® to treat acute HF. Limited preclinical data exists regarding the remaining three N-terminal peptides although all three have been explored for clinical utility in a limited series of Phase 1 and 2a clinical trials in the U.S. and in Australia. We have examined a 37 a.a. linear peptide, mid-sequence in the prohormone termed proANP 31-67 (MP3167) to better understand its role in CRS. MP3167 is unique among the four as it has the longest half-life of all in humans (1-1/2 hours vs. minutes), is highly acidic (pI=3.2; -5 net charge), appears resistant to degradation by neprilysin and has been reported to act through PGE2 although the tissue source in humans is unknown. We show for the first time that MP3167 elicits a 3-fold increase in PGE2 release over basal levels predominantly in human renal medullary tissue (from 2401 ± 97.2 to 8437 ± 62.9 pg/ml, N=3, p<0.001). The positive control, beta hydroxyl butyric acid (BOH) also increased PGe2 (from 2401 ± 97.2 to 7749 ±120 pg/ml, N=3, p<0.01). In 3D cultured cells isolated from digested tissue , we also observed an increase in MP3167 stimulated PGE2 (From 41.1 ± 1.3 to 62.9 ± 3.19 pg/ml, N=3, p<0.05). The PGE2 signal co-localizes with cells stained by L1-CAM antibody implicating collecting tubules/ducts at the cortical-medullary interface. As the receptor and second messenger pathway for MP3167 is unknown, we have isolated L1-CAM positive cells and created immortalized cell lines of human origin. Initial findings reiterate MP3167 stimulated PGE2 release, reaching a maximum by ~10 min. These human studies will enable better understanding of MP3167 as a regulator of renal function and the paracrine actions of PGE2 in rebalancing heart and renal function in CRS associated HF.

100 项与 Madeleine Pharmaceuticals Pty Ltd. 相关的药物交易

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100 项与 Madeleine Pharmaceuticals Pty Ltd. 相关的转化医学

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