title: Cyclic dinucleotide (c-di-GMP, c-di-AMP, and cGAMP) signalings have come of age to be inhibited by small molecules.
abstract: Bacteria utilize nucleotide-based second messengers to regulate a myriad of physiological processes. Cyclic dinucleotides have emerged as central regulators of bacterial physiology, controlling processes ranging from cell wall homeostasis to virulence production, and so far over thousands of manuscripts have provided biological insights into c-di-NMP signaling. The development of small molecule inhibitors of c-di-NMP signaling has significantly lagged behind. Recent developments in assays that allow for high-throughput screening of inhibitors suggest that the time is right for a concerted effort to identify inhibitors of these fascinating second messengers. Herein, we review c-di-NMP signaling and small molecules that have been developed to inhibit cyclic dinucleotide-related enzymes.
authors.affiliation: Department of Chemistry, Center for Drug Discovery, Purdue University, West Lafayette, IN 47907, USA. hsintim@purdue.edu.
authors.forename: Clement
authors.initials: C
authors.lastname: Opoku-Temeng
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Yue
authors.initials: Y
authors.lastname: Zheng
authors.forename: Jianmei
authors.initials: J
authors.lastname: Su
authors.forename: Herman O
authors.initials: HO
authors.lastname: Sintim
mesh_terms: D000242:Cyclic AMP / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006152:Cyclic GMP / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D009712:Nucleotides, Cyclic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D009712:Nucleotides, Cyclic; D054852:Small Molecule Libraries; C584311:cyclic guanosine monophosphate-adenosine monophosphate; D000242:Cyclic AMP; D006152:Cyclic GMP