The polypharmacology of natural products.

The once-popular approach of using natural products as a prime source for medicinal chemistry and drug discovery has waned considerably in the past two decades due to the advent of high-throughput screening of small molecule mega libraries. However, the growing appreciation of network pharmacology as the next drug-discovery paradigm suggests that natural products and their unique polypharmacology offer significant advantages for finding novel therapeutics particularly for the treatment of complex and multifactorial diseases. Drug discovery process is awaiting the revitalization of interest in natural products and their derivatives. The current challenge is how to decipher this natural chemical diversity.

One size does not fit all: Challenging some dogmas and taboos in drug discovery.

Advances in genetics, biology, chemical synthesis and computational methods have contributed to the understanding of diseases and drugs and with all of the above, there is an expectation that we are in a better position than ever before to create effective medicines for our needs. The reality is, however, disconnected from the expectation - US FDA drug approval statistics show that the number of approved drugs, especially the first-in-class drugs, is not commensurate with our improved knowledge. In this perspective, we offer our views on the possible reasons for this, focusing on small-molecule drugs and suggest some ideas for further considerations.

Clinical utility of neuroprotective agents in neurodegenerative diseases: current status of drug development for Alzheimer's, Parkinson's and Huntington's diseases, and amyotrophic lateral sclerosis.

INTRODUCTION: According to the definition of the Committee to Identify Neuroprotective Agents in Parkinson's Disease (CINAPS), "neuroprotection would be any intervention that favourably influences the disease process or underlying pathogenesis to produce enduring benefits for patients" [Meissner W, et al. Trends Pharmacol Sci 2004;25:249-253]. Preferably, neuroprotective agents should be used before or eventually during the prodromal phase of the diseases that could start decades before the appearance of symptoms. Although several symptomatic drugs are available, a disease-modifying agent is still elusive. AREAS COVERED: The aim of the present review is to give an overview of neuroprotective agents being currently investigated for the treatment of AD, PD, HD and ALS in clinical phases. EXPERT OPINION: Development of effective neuroprotective therapies resulting in clinically meaningful results is hampered by several factors in all research stages, both conceptual and methodological. Novel solutions might be offered by evaluation of new targets throughout clinical studies, therapies emerging from drug repositioning approaches, multi-target approaches and network pharmacology.