title: Lanthionine synthetase component C-like protein 2: a new drug target for inflammatory diseases and diabetes.
abstract: 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.
authors.forename: Pinyi
authors.initials: P
authors.lastname: Lu
authors.forename: Raquel
authors.initials: R
authors.lastname: Hontecillas
authors.forename: Casandra W
authors.initials: CW
authors.lastname: Philipson
authors.affiliation: Laboratory of Nutritional Immunology and Molecular Medicine Laboratory (www.nimml.org), Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, VA 24061, USA. jbassaga@vt.edu.
authors.forename: Josep
authors.initials: J
authors.lastname: Bassaganya-Riera
mesh_terms: D000040:Abscisic Acid / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D028044:Phosphate-Binding Proteins; D011487:Protein Conformation
chemical_list: D000893:Anti-Inflammatory Agents; D007004:Hypoglycemic Agents; C471704:LANCL2 protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; D028044:Phosphate-Binding Proteins; D000040:Abscisic Acid