Computer-aided drug design for AMP-activated protein kinase activators.

AMP-activated protein kinase (AMPK) is an important therapeutic target for the potential treatment of metabolic disorders, cardiovascular disease and cancer. Recently, various classes of compounds that activate AMPK by direct or indirect interactions have been reported. The importance of computer-aided drug design approaches in the search for potent activators of AMPK is now established, including structure-based design, ligand-based design, fragment-based design, as well as structural analysis. This review article highlights the computer-aided drug design approaches utilized to discover of activators targeting AMPK. The principles, advantages or limitation of the different methods are also being discussed together with examples of applications taken from the literatures.

Structure-based drug metabolism predictions for drug design.

Significant progress has been made in structure-based drug design by pharmaceutical companies at different stages of drug discovery such as identifying new hits, enhancing molecule binding affinity in hit-to-lead, and reducing toxicities in lead optimization. Drug metabolism is a major consideration for modifying drug clearance and also a primary source for drug metabolite-induced toxicity. With major cytochrome P450 structures identified and characterized recently, structure-based drug metabolism prediction becomes increasingly attractive. In silico methods based on molecular and quantum mechanics such as docking, molecular dynamics and ab initio chemical reactivity calculations bring us closer to understand drug metabolism and predict drug-drug interactions. In this study, we review important progress in drug metabolism and common in silico techniques adopted to predict drug regioselectivity, stereoselectivity, reactive metabolites, induction, inhibition and mechanism-based inactivation, as well as their implementation in hit-to-lead drug discovery.

Nuevos enfoques de las buenas prácticas de Manufactura / Good manufacturing practices new approaches

Durante los últimos años, el trabajo en Buenas Prácticas de Manufactura (bpm), además de contribuir a mejorar la calidad de los productos farmacéuticos disponibles en el mercado, ha permitido realizar un avance importante en la interpretación conceptual y en la aplicación práctica del verdadero significado del aseguramiento de la calidad en la industria farmacéutica. En ese sentido, este artículo analiza los aportes que sobre este tema han tenido las buenas prácticas de ingeniería, el desarrollo de producto, los programas de acciones correctivas y acciones preventivas, la gestión del riesgo en calidad, el control de procesos productivos en tiempo real y el sistema de gestión de la calidad para la industria farmacéutica. Sin duda, su adopción, que en la mayoría de los casos no corresponde a una exigencia explícita de la guía de bpm y que supone una inversión mayor de recursos, ofrece claros beneficios organizacionales y aporta evidencia para fortalecer la confianza, especialmente de las autoridades reguladoras, del cumplimiento del compromiso con la calidad que manifiesta una empresa determinada.

During the previous years, the Good Manufacturing Practices (gmp) work, besides contributing in improving the pharmaceutical products quality, has allowed an important progress in both the understanding and the practical application in the real meaning of the quality assurance in the pharmaceutical industry. As a contribution to this issue, this document studies the contributions of the good engineering practices, the product development, the corrective and preventive action system, the quality risk management, the process analytical technology and the pharmaceutical quality system. The implementation of these concepts, that in the majority of cases are not explicit gmp guide requirements, could suppose spending more money from the firm. However, on the contrary, it would give obvious benefits and contribute to have evidence, especially for the competent national authorities, about the fulfillment quality police implementation.

Computer-aided drug design: the next 20 years.

This perspectives article has been taken from a talk the author gave at the symposium in honor of Yvonne C. Martin's retirement, held at the American Chemical Society spring meeting in Chicago on March 25, 2007. The talk was intended as a somewhat lighthearted attempt to gaze into the future; inevitably, in print, things will come across more seriously than was intended. As we all know-the past is rarely predictive of the future.