title: Small molecules with anti-inflammatory properties in clinical development.
abstract: Inflammation is a crucial physiological response of our body to any kind of noxa be it an infection or tissue injury. However, this physiological process can be detrimental if dysregulated, and when the acute inflammatory response fails to resolve the cause of inflammation, there can be a switch to chronification. According to ICD 10 (WHO) over 3.000 diseases exist with the suffix "-itis" which terms an inflammatory disease. For the treatment of inflammation, non-steroidal anti-inflammatory drugs (NSAIDs) are the most widespread drugs while glucocorticoids are among our strongest weapons against inflammation, making them emergency treatments for acute episodes of chronic inflammation. For the treatment of many inflammatory disorders, both are not satisfying. Consequently, industrial and academic research on anti-inflammatory drugs is very intensive. In this review, we evaluate current treatments and unmet needs of chronic inflammatory diseases with high prevalence (rheumatoid arthritis, multiple sclerosis, chronic obstructive pulmonary disease, inflammatory bowel disease, and psoriasis), and systematically review small molecules with anti-inflammatory properties presently in clinical trials for the aforementioned diseases. As the pathophysiological knowledge of diseases increased over the last decades, a more specific intervention of inflammatory pathways becomes possible. After one hundred years of NSAIDs and over fifty years of glucocorticoids, more specific drugs for anti-inflammatory therapy such as roflumilast or fingolimod are rising. The aim of this article is to critically review the literature on small anti-inflammatory molecules in clinical trials to generate an idea of what we can expect in the future.
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany. Electronic address: hanke@pharmchem.uni-frankfurt.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hanke
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany. Electronic address: merk@pharmchem.uni-frankfurt.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Merk
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Steinhilber
authors.affiliation: Institute of Clinical Pharmacology, Pharmazentrum Frankfurt, LiFF/ZAFES, Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Schubert-Zsilavecz
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D009103:Multiple Sclerosis / Q000188:drug therapy; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy
chemical_list: D000893:Anti-Inflammatory Agents
keywords: Chronic obstructive pulmonary disease; Clinical trials; Inflammatory bowel diseases; Multiple sclerosis; Psoriasis; Rheumatoid arthritis