It was not shocking to learn that a number of combichem firms such as Discovery Partners International, ArQule, and Tripos are exiting or reducing scale of this once-glamorous business because of a downward trend. What is surprising is combichem's seemingly short life cycle. In just 10 years or so, combichem has been born, grown, reached the zenith, and gradually started facing challenges. The recent downsizing is probably the accumulated result of a quite complex combination of environmental factors, such as the general pressure pharmaceutical companies face from a highly competitive economy in which investment efficiency is the key to surviving and prospering and from a society that demands safer and more affordable medicine. And, more technically, from the disappointment of the naive expectation of what combichem could deliver. Looking back even five years, combichem and genomics were popular and fashionable words that companies and scientists wanted to be associated with. Now, some firms are starting to distance themselves or have become considerably less passionate about these two fields. As scientists, we know that the amazing developments in combichem and genomics, both technical and conceptual, have contributed to and are going to continue to greatly impact modern drug discovery. From its birth, as the direct result of information technology and automation, combichem has become a practice that is not limited to any particular technological platform and exists as parallel synthesis, array synthesis, library synthesis, and so on. The scale of operation may vary, but the concept has been widely accepted. Taking advantage of rapid advances in diverse purification techniques and the growing use of solid-phase reagents and microwave heating technology, both pharma and biotech companies are finding the applications that fit their discovery paradigm, while the practitioners in the field are perfecting their skills sets. The combichem tools are being applied broadly to all stages of drug discovery, file enrichment for corporate collection, lead generation, and lead optimization. The size of synthesized libraries is getting smaller and more focused, making the turnaround time shorter and shorter. Another encouraging development is the unprecedented selection of chemical starting materials from rapidly growing custom synthesis companies. In addition, there is a growing trend of outsourcing chemical activity to China and other emerging economies to maximize investment. Therefore, I deeply believe the boom may be gone and the emphasis is changing, but the influence will last. The recent shake-ups are just the inherent dynamism of this fast-moving economy. Let's hope that pharmaceutical companies will continue to efficiently discover innovative medicines, and that society will make a conceptual leap to recognize that to discover an effective and safe medicine is a formidable task. As such, society can continue to enjoy and appreciate the great advances in chemistry technology such as combichem. Combichem lives on! by Bolin Geng, Mass. C&EN News, 2006, 84, 2-3
