A pathway to next-generation mast cell stabilizers identified through the novel Phytomedical Analytics for Research...

Area of Science:

• Pharmacology and Bioinformatics
• Phytomedicine and Drug Discovery

Background:

• Mast cell stabilizers (MCS) offer potential for allergy and inflammation by suppressing mast cell responses, unlike antihistamines that only block histamine.
• Current MCS have limitations including poor bioavailability, frequent dosing, and unclear mechanisms, creating a need for new therapeutic options.
• Phytomedicine represents a rich source for novel mast cell stabilizers (ngMCS), with cromolyn sodium derived from Ammi visnaga as a precedent.

Purpose of the Study:

• To develop and validate a coupled pharmacoanalytic and in vitro pharmacology approach to identify and prioritize next-generation mast cell stabilizers (ngMCS) from phytomedical sources.
• To leverage a novel phytopharmacopeia data platform and advanced analytics to discover and derisk potential ngMCS candidates.
• To address unmet therapeutic needs in allergy, inflammation, and complex conditions like Mast Cell Activation Syndrome (MCAS).

Main Methods:

• Development of a comprehensive phytopharmacopeia data platform integrating >3.5 billion linkage pathways across biogeography, medical systems, and chemical components.
• Application of a novel data analytics workflow including druggability indices, target, and pathway analyses for candidate identification.
• Validation of selected phytomedical ngMCS candidates using in silico workflows and in vitro pharmacology, alongside development of a harmonic mean-based 'MCS score' for prioritization.

Main Results:

• A novel data analytics workflow and phytopharmacopeia data platform were established for identifying potential ngMCS.
• A subset of candidate phytomedical ngMCS was successfully validated using in silico and in vitro methods.
• A new 'MCS score' was developed to streamline the prioritization of promising ngMCS candidates.

Conclusions:

• The developed pharmacoanalytic and in vitro pharmacology approach is effective in identifying and validating novel mast cell stabilizers from phytomedical sources.
• This strategy holds significant potential for discovering next-generation mast cell stabilizers (ngMCS) to overcome limitations of current therapies.
• The findings are particularly relevant for complex conditions like Mast Cell Activation Syndrome (MCAS), suggesting ngMCS may offer superior management strategies.