Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Second-generation beta-oxidation resistant 3-oxa-lipoxin A4 analogs.

William J Guilford1, John F Parkinson

  • 1Department of Medicinal Chemistry, Berlex Biosciences, 2600 Hilltop Drive, Richmond, CA 94804, USA. william_guilford@berlex.com

Prostaglandins, Leukotrienes, and Essential Fatty Acids
|June 30, 2005
PubMed
Summary

New synthetic lipoxin analogs overcome rapid metabolism, showing potent anti-inflammatory effects. These stable compounds offer therapeutic potential for various inflammatory conditions and immune dysfunction.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Mechanistic aspects of inducible nitric oxide synthase-induced lung injury in burn trauma.

Burns : journal of the International Society for Burn Injuries·2011
Same author

Discovery of novel and potent aryl diamines as leukotriene A4 hydrolase inhibitors.

Bioorganic & medicinal chemistry letters·2008
Same author

Synthesis of N-alkyl glycine amides as potent inhibitors of leukotriene A4 hydrolase.

Bioorganic & medicinal chemistry letters·2008
Same author

Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A4 hydrolase.

Bioorganic & medicinal chemistry·2008
Same author

Mechanisms of intimal hyperplasia learned from a murine carotid artery ligation model.

Current vascular pharmacology·2008
Same author

Lipoxin A4 stable analogs reduce allergic airway responses via mechanisms distinct from CysLT1 receptor antagonism.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology·2007

Area of Science:

  • Biochemistry
  • Pharmacology
  • Immunology

Background:

  • Lipoxin A4 (LXA4) and aspirin-triggered 15-epi-LXA4 are potent anti-inflammatory eicosanoids.
  • Therapeutic application of LXA4 is limited by rapid in vivo metabolism and chemical instability.
  • First-generation analogs (e.g., ATLa) aimed to reduce omega-end metabolism.

Purpose of the Study:

  • To develop second-generation lipoxin analogs with improved pharmacokinetic properties.
  • To evaluate the anti-inflammatory potency and efficacy of these novel analogs.
  • To explore lipoxins as a therapeutic principle for inflammatory and immune disorders.

Main Methods:

  • Development of second-generation 3-oxa-LXA4 analogs.
  • Pharmacokinetic analysis to assess metabolic stability.

Related Experiment Videos

  • In vivo testing in various animal models of acute and chronic inflammation (e.g., skin edema, peritonitis, colitis).

    • Main Results:

    • Pharmacokinetic analysis revealed beta-oxidation as a novel LXA4 metabolic pathway.
    • Second-generation 3-oxa-LXA4 analogs demonstrated comparable potency and efficacy to ATLa.
    • These analogs showed efficacy via topical, intravenous, and oral delivery in multiple inflammatory models.
    • Remarkable once-daily oral efficacy in preventing and resolving TNBS-induced colitis.

    Conclusions:

    • Second-generation 3-oxa-LXA4 analogs possess improved pharmacokinetic disposition and stability.
    • These analogs are potent anti-inflammatory agents across diverse administration routes and models.
    • 3-oxa-LXA4 analogs represent promising pharmacophores for therapeutic strategies targeting inflammation and immune dysfunction.