According to the American Cancer Society, there were an estimated 1.68 million new cancer diagnoses in the United States in 2015 and nearly 600,000 cancer-related deaths. The family of five nuclear factor-kB (NF-kB) transcription factor proteins are implicated in carcinogenesis in almost all cancers, making them an attractive chemotherapy target. Cancer research laboratories have been pursuing NF-kB inhibitors for more than two decades. This technology describes a class of small molecule inhibitors of NF-kB proteins. Because of the ubiquity of NF-kB, they not only have potential as treatments for many different cancers, but also for autoimmune disorders and inflammatory disease.
NF-kB is associated with the transcription of more than 400 different genes, many of which are critical for cancer cell growth and survival. The inhibitors described by this technology are a class of N-(quinolin-8-yl)benzenesulfonamides. They were identified using high-throughput screening, and work by inhibiting the transport of one of the protein subunits of NF-kB into the nucleus of cells, which is where transcription of DNA occurs.
These inhibitors display micromolar activity in vitro and did not exhibit significant toxicity in mice, even at levels as high as 10 mg/kg. In addition, a murine model for aggressive lymphoma showed complete remission upon treatment with one analog described by this technology, which also inhibited tumor growth in a murine model with human DLBCL xenografts.
Patent Pending (US 20140073668)
Tech Ventures Reference: IR 2815