Table of Contents

March 2000
Vol. 3, No. 2

FEATURES
28	Playing the economics game with outsourcing John K. Borchardt Today's contract research organizations provide a range of services, such as early- and late-stage discovery, preclinical testing, all stages of clinical testing, postmarketing surveillance trials, manufacturing, sales, and marketing. Outsourcing to CROs will continue because of the increasing complexity of the drug development process, a growing number of global development projects, and the incentives of higher revenue gained through faster drug development.
37	Blocking HIV's "scissors" Jim Kling Central to the formation of new infectious virions, HIV protease cleaves the gag-pol protein into smaller fragments that form part of the core of the new particle. Even as new drugs grab the headlines, protease inhibitors such as Crixivan will continue to be known as the drugs that gave humanity the first true hope of conquering HIV.
46	Outsourcing the search for leads Hans Herklots Chemists must enrich their compound files so that more meaningful leads arise from high-throughput screening assays. Although cheminformatics is becoming more sophisticated and efficient at predicting what molecular structures give the best response as a drug candidate, scientists searching for lead compounds really need more chemistry, new molecular structures, and a richer chemical world from which to build a better compound file. Moreover, this rich new chemical world actually comes at an affordable price compared with the skyrocketing investments in combinatorial chemistry.
53	Polymorphic predictions Katriona Knapman Polymorphism, the ability of a molecule to crystallize into more than one crystal arrangement, can have a profound effect on the shelf life, solubility, formulation properties, and processing properties of a drug. Different polymorphs can have different rates of uptake in the body, leading to lower or higher biological activity than desired. In extreme cases, an undesired polymorph can even be toxic. If a company knows all of the possible polymorphs of a drug, it can foresee any potential problems in manufacturing and can also ensure greater patent protection for the drug.