Boron-based Polycystic Kidney Disease Therapy

This invention features novel compounds and a method of treatment to reduce cyst growth in Polycystic Kidney Disease (PKD). The compounds target a key cellular pathway involved in abnormal growth in PKD and other rapidly developing disorders, including cancer and neurological disorders. In PKD, numerous fluid-filled cysts are formed by the rapid production of tubule epithelial cells, resulting in massively enlarged kidneys and a progressive decline in renal function. There is no approved clinical therapy directed at the cellular defect responsible for PKD. This invention addresses the need for a new PKD treatment by the design, synthesis and development of novel ILK inhibitors.

Integrin-linked kinase (ILK) is a signaling molecule that bridges the communication between the extracellular matrix and cell signaling pathways through cell surface integrin. The inventors designed and synthesized specific binding compounds. These compounds target abnormal cell growth by reducing two specific kinds of signaling, both of which have been implicated in cyst growth in PKD and tumor growth in cancer. Initial drug screenings showed compounds inhibiting cell multiplication in small concentrations.

BENEFITS: 

• These inhibitors have higher efficacy, increased specificity, reduced toxicity and increased cell permeability compared to commercially available inhibitors, such as CPD-22
• Initial drug screenings showed compounds inhibiting cell growth

APPLICATIONS: 

• PKD
• Cancer
• Neurological disorder disease
• Ocular disease
• Other hyperproliferative diseases with aberrant ILK activity.
• Could also be used as novel radiosensitizers for many diseases with drug resistance
• Or as novel materials for drug delivery and imaging tools