Delving into the Latest Updates on ANX-042 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target-

Mechanism-

Therapeutic Areas

Cardiovascular DiseasesUrogenital Diseases

Active Indication

Cardio-Renal SyndromeHypotension

Inactive Indication-

Originator Organization

Mayo Clinic

Active Organization

Mayo Clinic

Inactive Organization

Anexon, Inc.

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

Login to view timeline

Gene Sequence

Sequence Code 976706

Endogenous natriuretic peptides serve as potent activators of particulate guanylyl cyclase receptors and the second messenger cGMP. Natriuretic peptides are essential in maintenance of volume homeostasis, and can be of myocardial, renal and endothelial origin. Advances in peptide engineering have permitted the ability to pursue highly innovative drug discovery strategies. This has resulted in designer natriuretic peptides that go beyond native peptides in efficacy, specificity, and resistance to enzymatic degradation. Together with recent improvements in peptide delivery systems, which have improved bioavailability, further advances in this field have been made. Therefore, designer natriuretic peptides with pleotropic actions together with strategies of chronic delivery have provided an unparalleled opportunity for the treatment of cardiovascular disease. In this review, we report the conceptual framework of peptide engineering of the natriuretic peptides that resulted in designer peptides for cardiovascular disease. We specifically provide an update on those currently in clinical trials for heart failure and hypertension, which include Cenderitide, ANX042 and ZD100.

07 Jul 2009·Proceedings of the National Academy of SciencesQ1 · CROSS-FIELD

Biodesign of a renal-protective peptide based on alternative splicing of B-type natriuretic peptide

Q1 · CROSS-FIELD

Article

Author: Pan, Shuchong ; Boerrigter, Guido ; Dickey, Deborah M. ; Potter, Lincoln R. ; Burnett, John C. ; Kleppe, Laurel S. ; Redfield, Margaret M. ; Lerman, Amir ; Simari, Robert D. ; Chen, Horng H. ; Lee, Candace ; Hall, Jennifer L.

Alternative RNA splicing may provide unique opportunities to identify drug targets and therapeutics. We identified an alternative spliced transcript for B-type natriuretic peptide (BNP) resulting from intronic retention. This transcript is present in failing human hearts and is reduced following mechanical unloading. The intron-retained transcript would generate a unique 34 amino acid (aa) carboxyl terminus while maintaining the remaining structure of native BNP. We generated antisera to this carboxyl terminus and identified immunoreactivity in failing human heart tissue. The alternatively spliced peptide (ASBNP) was synthesized and unlike BNP, failed to stimulate cGMP in vascular cells or vasorelax preconstricted arterial rings. This suggests that ASBNP may lack the dose-limiting effects of recombinant BNP. Given structural considerations, a carboxyl-terminal truncated form of ASBNP was generated (ASBNP.1) and was determined to retain the ability of BNP to stimulate cGMP in canine glomerular isolates and cultured human mesangial cells but lacked similar effects in vascular cells. In a canine-pacing model of heart failure, systemic infusion of ASBNP.1 did not alter mean arterial pressure but increased the glomerular filtration rate (GFR), suppressed plasma renin and angiotensin, while inducing natriuresis and diuresis. Consistent with its distinct in vivo effects, the activity of ASBNP.1 may not be explained through binding and activation of NPR-A or NPR-B. Thus, the biodesigner peptide ASBNP.1 enhances GFR associated with heart failure while lacking the vasoactive properties of BNP. These findings demonstrate that peptides with unique properties may be designed based on products of alternatively splicing.

100 Deals associated with ANX-042

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Cardio-Renal Syndrome	Phase 1	US	Mayo Clinic	01 Jan 2017
Hypotension	Phase 1	US	Mayo Clinic	01 Jan 2017
Heart Failure	Preclinical	US	Anexon, Inc.	-
Kidney Diseases	Preclinical	US	Anexon, Inc.	-