In the current review, we discuss the role of NF-κB and JAK/STAT signaling pathways and their small molecule regulators in the therapy of inflammatory diseases. Considering potential harmful effects directly assigned to the COX-2 inhibition, novel therapeutically-relevant biological targets such as NF-κB and JAK/STAT signaling pathways have received a growing attention. Here we summarize recent progress in the identification and development of novel, clinically approved or evaluated small molecule regulators of these signaling cascades as promising anti-inflammatory therapeutics. In addition, we illustrate key structural modifications and bioisosteric transformations among these inhibitors to provide a helpful basis for further development of novel small molecule anti-inflammatory agents.
Keywords: NF-κB, JAK/STAT, signalling, inhibitors, anti-inflammatory, therapy, Chronic inflammation, rheumatoid arthritis, ischaemic heart disease, atherosclerosis, cancer, fibrosis, Hayfever, Alzheimer's diseases, MAPKs, STAT, NSAIDs, Valdecoxib, leukemia, inflammatory bowel disease, arthritis, sepsis, asthma, multiple sclerosis, colitis, diabetic neuropathy, AIDS, GPCR, TNFR, NEMO, oxycodone/ibuprofen, Oxycodone, Bortezomib, RS-411, Fumaderm, Gabexate, MK-231, Silibinin, ST-1482, RK-0202, Salazosulfapyridine, Curaxin CBLC-102, NGX-3781, Hydrocodone, NSC-49171, Pseudoephedrine, T-614, Curcumin, MPC-7869, Dimethyl fumarate, Famotidine, Fluasterone, Tepoxalin, E-3330, EGCG, Declopramide, Resveratrol, Tranexamic acid, RTA-402, Orazipone, RTA-401, ALS-357, IMD-0354, SIM-688, ENMD-1198, Parthenolide, Cepharanthine, Taxifolin, SC-514, TPCA-1, BMS-345541, ML120B, HUVECs, RHEC, HMGB1, lung lavage, neutrophil influx, lung edema, SOCS, PIAS, Lestaurtinib, MHCII, HWA-486, CP-690550, MK-0457, TG-101348, LS-104, SKI-606, Atiprimod, ABT-869, mixed lymphocyte reaction, mycophenolate mofetil