title: Opportunities and Challenges for Fatty Acid Mimetics in Drug Discovery.
abstract: Fatty acids beyond their role as an endogenous energy source and storage are increasingly considered as signaling molecules regulating various physiological effects in metabolism and inflammation. Accordingly, the molecular targets involved in formation and physiological activities of fatty acids hold significant therapeutic potential. A number of these fatty acid targets are addressed by some of the oldest and most widely used drugs such as cyclooxygenase inhibiting NSAIDs, whereas others remain unexploited. Compounds orthosterically binding to proteins that endogenously bind fatty acids are considered as fatty acid mimetics. On the basis of their structural resemblance, fatty acid mimetics constitute a family of bioactive compounds showing specific binding thermodynamics and following similar pharmacokinetic mechanisms. This perspective systematically evaluates targets for fatty acid mimetics, investigates their common structural characteristics, and highlights demands in their discovery and design. In summary, fatty acid mimetics share particularly favorable characteristics justifying the conclusion that their therapeutic potential vastly outweighs the challenges in their design.
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt , Max-von-Laue-Straße 9, 60438 Frankfurt, Germany.
authors.forename: Ewgenij
authors.identifier: 0000-0003-1961-1859
authors.initials: E
authors.lastname: Proschak
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt , Max-von-Laue-Straße 9, 60438 Frankfurt, Germany.
authors.forename: Pascal
authors.initials: P
authors.lastname: Heitel
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt , Max-von-Laue-Straße 9, 60438 Frankfurt, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Kalinowsky
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt , Max-von-Laue-Straße 9, 60438 Frankfurt, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Merk
mesh_terms: D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D055808:Drug Discovery; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008958:Models, Molecular
chemical_list: D016861:Cyclooxygenase Inhibitors; D005227:Fatty Acids