Multicenter, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy/Safety of CY-1503 (Cylexin) in Prevention of Reperfusion Injury in Neonates/Infants Undergoing Hypothermic Cardiopulmonary Bypass

We conducted a multicenter, randomized, placebo-controlled trial of Cylexin, an inhibitor of the attachment of white blood cells to the endothelium. Our study population was neonates and infants undergoing hypothermic cardiopulmonary bypass during surgical repair or palliation of congenital heart defects.

Start Date01 Dec 1997

Sponsor / Collaborator

The Children's Hospital Corp.

100 Clinical Results associated with CY-1503

100 Translational Medicine associated with CY-1503

100 Patents (Medical) associated with CY-1503

Literatures (Medical) associated with CY-1503

01 Jan 2005·Treatments in Respiratory Medicine

Therapeutic Potential in Asthma and COPD

Review

Author: Romano, Suzanne J

Asthma and COPD are chronic inflammatory conditions that affect hundreds of millions of patients worldwide. New therapeutics are desperately needed, especially those that target the underlying causes and prevent disease progression. Although asthma and COPD have distinct etiologies, both are associated with reduced airflow caused by excess infiltration of inflammatory cells into healthy lung tissues. As selectin-mediated adhesion of leukocytes to the vascular endothelium is a key early event in the initiation of the inflammatory response, selectin inhibition is thought to be a good target for therapeutic intervention. Three known selectins are expressed in distinct subsets of cells: P-selectin is presented on the surface of activated platelets and endothelial cells, L-selectin is constitutively expressed on leukocytes, and E-selectin synthesis is upregulated in activated endothelial cells. They mediate cell-cell adhesion in the shear flow of the bloodstream via specialized interactions with clusters of oligosaccharides presented on cell surface glycopeptide ligands. The role of selectin-ligand interactions in the inflammatory response has been demonstrated in various animal models, prompting considerable attention from the pharmaceutical industry.Drug discovery efforts have yielded many different classes of selectin inhibitors, including soluble protein ligands, antibodies, oligosaccharides and small molecules. Although many selectin inhibitors have shown activity in preclinical models, clinical progress of selectin-directed therapies has been slow. Early approaches employed carbohydrate-based inhibitors to mimic the natural ligand sialyl Lewis X; however, these compounds proved challenging to develop. Cytel's CY 1503, a complex oligosaccharide, progressed to phase II/III trials for reperfusion injury, but further development was halted when it failed to demonstrate clinical efficacy. Two protein-based selectin inhibitors have reached phase II development. These included Wyeth's recombinant soluble P-selectin ligand, TSI (PSGL-1), which was discontinued after disappointing results in myocardial infarction trials and Protein Design Labs' humanized anti-L-selectin monoclonal antibody, which is currently in development for trauma. Bimosiamose, discovered by Encysive Pharmaceutical and presently being developed by Revotar Biopharmaceuticals, is an 863 g/mol molecular weight dimer with minimal carbohydrate content and is, to date, the leading selectin inhibitor in clinical development. This compound has shown promise in a phase IIa 'proof of concept' trial in patients with asthma, reducing airway recruitment of eosinophils after intravenous administration. Further clinical development of an inhaled formulation is underway. Despite a significant need for new therapeutics, selectin inhibitors have not yet been explored for the treatment of COPD. Bimosiamose represents an important proof of principle, and hopefully continued success will spark renewed interest in selectin-directed therapeutics for respiratory diseases.

01 Sep 2000·The Annals of Thoracic SurgeryQ2 · MEDICINE

Sialyl LewisX oligosaccharide preserves myocardial and endothelial function during cardioplegic ischemia

Q2 · MEDICINE

Article

Author: David P Nelson ; John E Mayer ; Elizabeth D Blume ; Laurie Phillips ; Marc L Schermerhorn

BACKGROUNDNeutrophil adhesion to endothelium contributes to myocardial reperfusion injury after cardiac operation. Initial neutrophil-endothelial interactions involve selectins, which bind Sialyl-LewisX on neutrophils. Blockade of selectin-mediated neutrophil-endothelial interactions with CY-1503, a synthetic analogue of Sialyl-LewisX, might reduce reperfusion injury after myocardial ischemia.METHODSThe efficacy of CY-1503 to attenuate global myocardial reperfusion injury was assessed in isolated blood-perfused neonatal lamb hearts that had 2 hours of cold cardioplegic ischemia. CY-1503 (40 mg/L) or saline vehicle was added to blood perfusate before ischemia. Contractile function (developed pressure, dP/dt) and coronary vascular endothelial function (acetylcholine response) were assessed at base line and during reperfusion. Myocardial neutrophil accumulation was assessed by myeloperoxidase quantification.RESULTSCompared to controls, treatment with CY-1503 improved recovery of all indices of contractile function, preserved coronary vascular endothelial function, and reduced myocardial neutrophil accumulation.CONCLUSIONSIn isolated neonatal lamb hearts that underwent hypothermic cardioplegic ischemia, CY-1503 administration reduced myocardial neutrophil accumulation and preserved endothelial and contractile function. Selectin blockade of leukocyte-endothelial interactions might attenuate reperfusion injury and enhance myocardial protection during cardiac surgical procedures.

01 Aug 2000·The Journal of Thoracic and Cardiovascular SurgeryQ1 · MEDICINE

Sialyl LewisX oligosaccharide preserves cardiopulmonary and endothelial function after hypothermic circulatory arrest in lambs

Q1 · MEDICINE

Article

Author: Hickey, Paul R. ; Mayer, John E. Jr. ; Khoury, Philip R. ; Tofukuji, Motohisa ; Nelson, David P. ; Sellke, Frank W. ; Phillips, Laurie ; Schermerhorn, Marc L.

OBJECTIVENeutrophil adhesion to endothelium contributes to cardiopulmonary dysfunction after cardiac surgical procedures. Initial neutrophil-endothelial interactions involve selectins, which bind carbohydrate ligands, such as sialyl-Lewis(X). Blockade of selectin-mediated neutrophil interactions with CY1503, a synthetic oligosaccharide analog of sialyl-Lewis(X), could limit neutrophil-mediated injury after cardiopulmonary bypass.METHODSThe efficacy of CY1503 treatment was tested in a lamb model of cardiopulmonary bypass with hypothermic circulatory arrest. Neonatal lambs received CY1503 (n = 6, CPB-CY1503) or saline solution vehicle (n = 7, CPB-saline) into the pump prime before bypass and as a continuous infusion throughout reperfusion. Five lambs served as control animals for in vitro microvessel studies. Indexes of myocardial function (preload recruitable stroke work index, and rate of pressure rise) and pulmonary function (compliance, airway resistance, and arterial PO (2)) were measured before bypass and during reperfusion. The effect of CY1503 on endothelium-dependent vascular reactivity was assessed by means of in vitro pulmonary and coronary microvessel studies.RESULTSMyocardial function was depressed after circulatory arrest, but CY1503 preserved function near baseline (36% +/- 25% vs 99% +/- 19% of baseline at 3 hours of reperfusion). CY1503-treated animals also demonstrated improved pulmonary function during reperfusion. In vitro microvessel analysis of vascular reactivity revealed endothelial dysfunction after circulatory arrest compared with control lambs. CY1503-treated lambs (CPB-CY1503) had intact endothelial function, as demonstrated by normal vasodilatory responses to endothelium-dependent vasodilators.CONCLUSIONSCY1503 preserves cardiopulmonary and endothelial function after cardiopulmonary bypass and hypothermic circulatory arrest in neonatal lambs. This suggests a role for selectin-mediated, neutrophil-endothelial interactions in the inflammatory response after cardiac operations.

100 Deals associated with CY-1503

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Reperfusion Injury	Phase 3	CA	-	-
Reperfusion Injury	Phase 3	US	Epimmune, Inc.	-
Reperfusion Injury	Phase 3	-	Sumitomo Pharma Co., Ltd.	-
Respiratory Diseases	Phase 3	US	Epimmune, Inc.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

CY-1503

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation