oa Editorial (A New Era for Medicinal Chemistry)

Expiration of some of the most profitable patents sustaining major pharmaceutical companies has been greeted with concern for the research pipeline. Yet, have the resources delivered innovation? Rational drug design has been followed with high throughput screening, neither living up to expectations. The quest for novelty has led back to fundamentals on lessons from academia and nature. While not the daring departure from the past, hoped for a decade ago with ‘high-tech solutions’, efforts resting on a firm foundation are essential to unraveling the web of complexity of chronic disease that now grips the industrialized world and is rapidly spreading to the developing world. Alzheimer disease, metabolic syndrome/diabetes, arthritis, and heart disease now define morbidity and mortality. While intervention at single points can offer some relief, it is at best to slow the process. Regenerative medicine may offer hope of renewal, but it may also fall short due to a poor understanding of system failure, or better stated, altered system homeostasis and reconfiguration, during aging and disease. Aging touches each of us, not just in decreased function, but in altered perspective, cognitively and fundamentally. Pleotrophic regulatory alterations are essential to maintaining evolutionarily acceptable function as we age. Intervention to disrupt these complex adaptations can deleteriously affect the course of aging as we have seen with anti-oxidant and antiamyloid therapies that disregard the biology driving disease. Therapeutics aligned to biology will be more effective. Fundamentals of biology: physiology, biochemistry, cell biology and yes evolutionary biology, must be brought to the table of medicinal chemistry.