Lanthionine Synthetase Component C-Like Protein 2: A New Drug Target for Inflammatory Diseases and Diabetes
Casandra W. Philipson,
Lanthionine synthetase component C-like protein 2 (LANCL2) is a member of the LANCL protein family,
which is broadly expressed throughout the body. LANCL2 is the molecular target of abscisic acid (ABA), a compound
with insulin-sensitizing and immune modulatory actions. LANCL2 is required for membrane binding and signaling of
ABA in immune cells. Direct binding of ABA to LANCL2 was predicted in silico using molecular modeling approaches
and validated experimentally using ligand-binding assays and kinetic surface plasmon resonance studies. The therapeutic
potential of the LANCL2 pathway ranges from increasing cellular sensitivity to anticancer drugs, insulin-sensitizing effects
and modulating immune and inflammatory responses in the context of immune-mediated and infectious diseases. A
case for LANCL2-based drug discovery and development is also illustrated by the anti-inflammatory activity of novel
LANCL2 ligands such as NSC61610 against inflammatory bowel disease and influenza-driven inflammation in mice.
This review discusses the value of LANCL2 as a novel therapeutic target for the discovery and development of new
classes of orally active drugs against chronic metabolic, immune-mediated and infectious diseases.
Keywords: ABA, drug discovery, inflammation, LANCL2, molecular modeling, target.
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