Columbia Technology Ventures

Compounds to inhibit BACE1 and NF-kB activity

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.

Sulfonamides as low-cost, versatile, and efficient inhibitors of BACE1 and NF-kB activity

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.

Lead Inventor:

Donald W. Landry, M.D., Ph.D.

Applications:

  • Treatment or preventative measure for Alzheimer's disease
  • Treatment for neurodegenerative disease and related conditions
  • Treatment of diseases related to dysfunction of cell proliferation
  • Treatment of immune system or inflammatory diseases
  • Possible NF-kB-targeting cancer therapeutics
  • Reagents for basic BACE1/NF-kB research
  • Secondary indication as an erectile dysfunction treatment

Advantages:

  • Highly efficient 'one-pot' synthesis method
  • Utilizes mild reaction conditions
  • Minimal purification required and good yield of desired compound
  • Targets two proteins with well-characterized roles in various diseases.

Patent Information:

Patent Pending (US 20140275165)

Patent Pending (US20110071124)

Tech Ventures Reference: IR 2438

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