Nucleotide-binding oligomerization domain (NOD) inhibitors: a rational approach toward inhibition of NOD signaling pathway.
Dysregulation of nucleotide-binding oligomerization domains 1 and 2 (NOD1 and NOD2) has been implicated in the pathology of various inflammatory disorders, rendering them and their downstream signaling proteins potential therapeutic targets. Selective inhibition of NOD1 and NOD2 signaling could be advantageous in treating many acute and chronic diseases; therefore, harnessing the full potential of NOD inhibitors is a key topic in medicinal chemistry. Although they are among the best studied NOD-like receptors (NLRs), the therapeutic potential of pharmacological modulation of NOD1 and NOD2 is largely unexplored. This review is focused on the scientific progress in the field of NOD inhibitors over the past decade, including the recently reported selective inhibitors of NOD1 and NOD2. In addition, the potential approaches to inhibition of NOD signaling as well as the advantages and disadvantages linked with inhibition of NOD signaling are discussed. Finally, the potential directions for drug discovery are also discussed.
Faculty of Pharmacy, University of Ljubljana , Aškerčeva 7, SI-1000 Ljubljana, Slovenia.
Žiga
Ž
Jakopin
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy / Q000209:etiology; D003424:Crohn Disease / Q000188:drug therapy / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D058990:Molecular Targeted Therapy / Q000379:methods; D053474:Nod1 Signaling Adaptor Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D015398:Signal Transduction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein