Selective Inhibitor Of Cathepsin K Design, Synthesis And Screening

Osteoporosis is a disease characterized by an imbalance between bone resorption and formation. Excessive bone resorption causes changes in the microstructure of the bone matrix which makes bones prone to fracture. In 1990, an estimated 1.7 million osteoporosis-related hip fractures occurred worldwide from which approximately 25% had a lethal outcome. Currently, 44 million people or 55% of the US population aged 50 or older have osteoporosis or are at risk to develop the condition during their lifespan. Direct and indirect costs of osteoporosis are staggering and estimated to be $18 billion annually and increasing every year. Current therapies are mostly directed to decrease the rate of bone resorption. All therapies show efficacy but reveal various problems.Al lstudies shows the major proteolytic activity of osteoclasts is cathepsin K which represents 98% of the total cysteine protease activity.Thus primary reason leading to the Osteoporosis is the over-express of cathepsin K.Fourteenanalogs of E64d were synthesize,among which thirteen new were new structurally peptides.The screening results showed that there were six of the E64d analogs exhibiting inhibition significantly.