Anti-inflammatory compounds for dermatology and chronic inflammation

Background

While inflammation is a beneficial component of the body’s response to harmful stimuli, prolonged or excessive inflammation triggers a wide variety of diseases. Current anti-inflammatory drugs (steroids, NSAIDs and immune selective anti-inflammatory derivatives) have undesirable side effects and for many indications including dermatology, drugs that act by a novel MOA may be more efficacious.

Technology Description

Scientists at Scripps Institute of Oceanography have purified and validated the utility of honaucin A (from the cyanobacteria Leptolyngbya crossbyana) for dermatologic indications and other inflammatory conditions. The dual MOA vs. inflammation and bacterial infection make honaucins particularly interesting for diseases that are characterized by features of inflammation and infection. Synthesis of honaucin and numerous analogs enabled SAR analysis, which revealed essential structural features for activities of interest and provided analogs with greater potency in bio-assays that assess inhibition of inflammation.

Applications

• Psoriasis and other inflammatory/infection-based dermatologic applications;
• trauma, including surgical trauma; and
• autoimmune diseases, such as rheumatoid arthritis.

Advantages

• An efficient, 2-step synthetic method supports large-scale manufacturing;
• In vivo and in vitro bioassays validate potent anti-inflammatory activity with limited cytotoxicity;
• A unique structure shows dual modes of action via inflammatory and quorum sensing pathways;
• Cytokine measurements of treated cells reveal an extremely attractive profile for an anti-inflammatory drug; and
• The NRF2-ARE pathway is activated at lower concentrations then with Tecfidera (FDA approved, dimethyl-fumarate)

State Of Development

•  In vivo validation in a murine model of inflammation substantiates in vitro studies with regard to dermatologic applications.
• Identification of the MOA (inhibiting KEAP-1 activates NRF2 (a transcription factor) which activates a number of known anti-inflammatory and cytoprotective genes.
• Potent inhibition of lipopolysaccharide‐stimulated NO2production in murine macrophages and of the quorum sensing‐dependentphenotype in Vibrio harveyi BB120.
• A decrease in NO2 production is accompanied by a decrease in the production of several pro‐inflammatory cytokines (IL-1, IL-6, TNF-alpha and iNOS).

Intellectual Property Info

US issued patent for “Anti-Inflammatory and Quorum Sensing Inhibition Compounds and Methods of Making and Using Them” available for exclusive licensure.

Related Materials

• Sapkota M, et al. (2015) Bromo-honaucin A inhibits osteoclastogenic differentiation in RAW 264.7 cells via Akt and ERK signaling pathways., Eur J Pharmacol., 769:100-9. - 12/15/2015
• Choi, H. et al. (2012) Honaucins A-C, potent inhibitors of inflammation and bacterial quorum sensing: synthetic derivatives and structure-activity relationships, Chem Biol. 19(5):589-98. - 05/25/2012
• See http://www.marinebiotech.org/gerwick.html

Patent Status