Nuclear factor-kappa B (NF-kB) is the transcription factor which is involved in the regulation of over 500 genes, and is responsible for cell proliferation, survival, invasion, metastasis, angiogenesis, and inflammation. Therefore, the development of therapeutics that acts as NF-kB inhibitors, can treat various diseases including cancer and chronic inflammation. Although, many different NF-kB inhibitors are reported, still there are no marketed drugs available.
NF-kB inhibitors act on NF-kB signaling at different levels, including at upstream of I-kB kinase (IKK) (for instance, at a receptor or adaptor level), directly at the IKK complex or I-kB phosphorylation, during ubiquitination or proteasomal degradation of I-kB, during nuclear translocation of NF-kB, NF-kB DNA binding, and NF-kB-directed gene transactivation. The level at which the drug candidate inhibits the NF-kB signaling pathway is simportant for better efficacy and helps to reduce adverse events.
NF-KB INHIBITORS DRUG CANDIDATES UNDER DEVELOPMENT (2017)
Many drugs have been identified that indirectly act as NF-kB inhibitors, including Fluvastatin, Carbocysteine, Ritonavir, Rapamycin, Raloxifene, and others. Their indirect targeting can be the result of crosstalk between their primary targets with the NF-kB signaling pathway.
Drug manufacturing companies are constantly involved in the quest to find better and new treatment strategies by targeting NF-kB which can be effective in various indications including cancer and chronic inflammation treatment. Various companies are developing drug candidates using different technologies for the development of effective and better drugs, which is driving the growth of the pipeline.
As of September 2017, the NF-kB inhibitors therapeutics pipeline comprises of approximately 17 drug candidates in different stages of development.
Some of the key players developing drugs as NF-kB inhibitors for the treatment of various indications include Alkermes Plc, Reata Pharmaceuticals, Inc., Incuron LLC, Catabasis Pharmaceuticals, Inc. and others.