Current Topics in Medicinal Chemistry - Volume 5, Issue 16, 2005

Due to factors such as resistance and long-term side effects as well as dosing regimen-related adherence issues, HIV therapy is a constantly moving target. HIV-1 protease inhibitors had an immediate and dramatic impact on the outcome of HIV/AIDS when launched in late 1995, and the search for new and improved next generation molecules has been under way in many laboratories. At GlaxoSmithKline (GSK) and Verte Read More

The amyloid-β (Aβ) peptide is the principal components of the senile plaques found in the brains of patients with Alzheimer's disease (AD). The poorly soluble 40-42 amino acid peptide, formed from the cleavage of the Ab precursor protein (APP) by two proteases, is believed to play a central role in the pathogenesis of AD. β-Secretase (memapsin 2, BACE1), a membrane-anchored aspartic protease, is responsible for the initial Read More

Prevalence of type 2 diabetes has increased dramatically in the last decades. Current medicines are not yet capable to efficiently prevent or reverse progression of the disease and its associated comorbidities. As a consequence, there is a great need for novel antidiabetic drugs. Treatments of type 2 diabetes that are based on enhanced and sustained action of insulinotropic incretin hormones such as GLP-1 have Read More

Osteoporosis is a progressive, debilitating bone disease resulting in increased cost and morbidity to the elderly. This review summarizes the therapeutic approaches taken in the treatment of osteoporosis with particular emphasis on cathepsin K inhibitors. Cathepsin K, a cysteine protease predominantly expressed in osteoclasts, is a key player involved in bone matrix degradation. Both genetic ablation and small molecule in Read More

Venous thromboembolic disease, including deep vein thrombosis and pulmonary embolism, is a cause of significant mortality and morbidity. For several decades, anticoagulant options for the treatment and prevention of thrombosis have been limited mainly to agents such as unfractionated heparin and oral vitamin K antagonists such as warfarin. Although these therapies have proven benefits, they also have important limita Read More

Caspase inhibition has been demonstrated to be therapeutically effective in moderating excessive programmed cell death, or apoptosis. Publications detailing programs in the pharmaceutical industry have been more frequent in recent years, ranging from SAR studies to clinically relevant animal models of disease. A summary of the work published in this exciting new area is presented, outlining the broad applicabi Read More