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Synthetic peptide

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Synthetic peptide	1

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MAPKAPK2(MAP kinase-activated protein kinase 2)	1

Background: Pre-clinical studies demonstrate anti-inflammatory and anti-fibrotic properties of MMI-0100, a peptide inhibitor of mitogen-activated protein kinase-activated protein kinase II (MK2). Aims: Phase I double blind randomised multiple dose (2.25mg od, 5 days) 2-way cross-over study to compare the effects of inhaled MMI-0100 with placebo on induced sputum inflammatory markers after LPS challenge. Methods: Induced sputum collected 6hrs post LPS challenge Day5; inflammatory biomarkers IL-1β, IL-6, IL-8, TNFα, sputum cell counts. FACS analysis of MK2 phosphorylation in induced sputum Day3. Results: 22 subjects randomised (ITT analysis); 16 subjects completed per protocol sputum analysis; no difference between treated and placebo groups on primary sputum biomarkers; ratios (MMI-0100/placebo): IL1β=0.639, IL8=0.909, TNFα=0.887, IL6=1.044. MK2 phosphorylation in sputum was consistent with inhibitory drug effect (trend but did not achieve statistical significance). No adverse events or effect on lung function. Post hoc analysis defined 9/16 subjects as MMI-0100 9responders9 (>25% decrease in sputum IL-1β). Responders had reductions in greater than half the selected biomarkers. Subjects mounting more robust inflammatory responses to LPS (placebo period) exhibited anti-inflammatory responses to MMI-0100. Conclusion: Low dose inhaled MMI-0100 did not show consistent effect on sputum inflammatory biomarkers post LPS challenge. However, a subject subgroup showed evidence of both pharmacological (FACS analysis) and pharmacodynamic effects (sputum biomarkers). Data suggest further studies should be performed at higher doses.

01 Sep 2016·3.2 Airway Cell Biology and Immunopathology

MAPKAP kinase 2(MK2) expression is associated with severe asthma

Author: Geoffrey Chupp ; Williamson Bradford ; Lauren Cohn ; Vera Nezgovorova ; Nicole Grant ; Xiting Yan ; Colleen Brophy

Introduction: The p38 Mitogen-Activated Protein Kinase pathway is dysregulated in asthma. MK2 is a p38 terminal kinase that regulates multiple asthma relevant genes(e.g. ALOX5, TNF-a, IL-6, dendritic cell Toll-like receptors), but its role in human asthma is unknown. We hypothesized MK2 expression is increased in asthma. Methods: Whole transcriptome gene expression profiles in sputum and blood were measured(Affymetrix ST 1.0) from 112 asthmatics and 12 controls. MK2 gene expression was correlated with clinical, physiologic and inflammatory disease characteristics. Results: Sputum MK2 gene expression was increased in asthmatics vs. controls(p=0.04) and correlated positively with lifetime hospitalizations(p=0.03) and Severe Asthma Research Program(SARP) cluster designation, and negatively with serum IgE levels(r=-0.28,p Conclusions: Sputum MK2 gene expression is significantly elevated in asthma, associated with poor lung function, neutrophilic inflammation and increased sputum chitinase activity. These data suggest MK2 mediates airway inflammation in asthma, particularly in severe phenotypes of disease, and warrants investigation as a therapeutic target.

01 May 2013·Arteriosclerosis, Thrombosis, and Vascular Biology

Abstract 204: Brilliant Blue FCF is an Alternative Vein Marking Dye That Restores Functional Viability in Human Saphenous Vien Graft

Author: Lander, Cynthia ; Brophy, Colleen ; Komalavilas, Padmini ; Cheung-Flynn, Joyce ; Hocking, Kyle M

ObjectiveThe human saphenous vein (HSV) is the most effective conduit for infrainguinal peripheral bypass grafting. Optimal vein graft preparation is critical to vein graft patency. Graft marking using surgical skin markers is detrimental to endothelial and smooth muscle function of the graft. The objective of this study was to evaluate the effect of FD&C Brilliant Blue No. 1 (FCF) as an alternative for vein graft marking.MethodsSegments of HSV were collected after typical harvest and graft preparation. The tissues were cut into rings and either left unmarked or marked with FCF (2.6 mM). The functional viability of the rings was determined in a muscle bath.Results Marking with FCF did not impair contractility of the smooth muscle (Figure 1A). Contractility was restored in HSV segments that had no functional contractile responses after harvest and preparation (Figure 1B). To determine the mechanism of this protective effect of FCF, purinergic receptors were activated with BzATP with and without pre-incubation with FCF (50μM) or a purinergic receptor antagonist (oATP, control) and the rise in [Ca 2+ ] i was measured. FCF and oATP reduced the BZATP-evoked rise in [Ca 2+ ] i (Figure 1C), suggesting that the salutary effects of FCF were due to inhibition of a P2X or P2Y receptor. ConclusionsFCF is a non-toxic alternative to surgical skin markers that antagonizes purinergic receptors in HSV. FCF restored functional viability to injured vascular smooth muscle. FCF may protect HSV against injury-elicited ‘danger’ signals such as extracellular ATP that is released during injury-induced preparation.

100 Deals associated with Moerae Matrix, Inc.

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100 Translational Medicine associated with Moerae Matrix, Inc.

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Pipeline

Pipeline Snapshot as of 10 May 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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