This technology describes a class of small molecule compounds called sulfonamides that are capable of modulating the activity of beta-secretase 1 (BACE1) and nuclear factor-kB (NF-kB). BACE1 is an enzyme involved in the production of amyloid beta, which has been linked to neurodegeneration and Alzheimer's disease, while NF-kB signaling is involved in inflammatory responses, oncogenesis, viral infection, and regulation of cell proliferation during immune responses. As such, these compounds may be developed as therapeutics for the treatment, prevention, or amelioration of neurodegenerative diseases, such as Alzheimer's disease, as well as diseases related to the dysfunction of cell proliferation, the immune system, or inflammation, including cancer. Furthermore, this technology also includes a method of quickly generating sufficient quantities of these compounds with minimal effort, maximizing the cost-efficiency of producing these compounds.
This technology efficiently inhibits two crucial proteins with one class of compounds. Compounds were initially screened using ELISA assays and high throughput methods: lead candidates for BACE1 inhibitors were tested on their ability to reduce sAPPβ levels, the key precursor of amyloid beta, while nuclear translocation and other factors were considered for NF-kB inhibitors. Sulfonamides (alkyl and benzene conjugated, respectively) emerged as putative inhibitors from both screens, suggesting great versatility. The compounds were synthesized using a new, 'one-pot' synthesis route that simplifies the production process and allows for many diverse ring substitutions. The synthesis technique is performed under mild reaction conditions and results in good yield without extensive purification, demonstrating safety and cost-efficiency.
These compounds have demonstrated great efficacy in previous pharmacological experiments, reducing both BACE1 and NF-kB activity with good potency.
Patent Pending (US 20140275165)
Patent Pending (US20110071124)
Tech Ventures Reference: IR 2438