Small molecule drug discovery in the fast-changing world of biotechnology

Generally referred to as Europe's largest Biotech company, Serono, with global headquarters in Geneva, has long been known for its portfolio of therapeutic proteins, which has, so far, resulted in market approvals of several recombinant products in the areas of reproductive health (Gonal-F, Luveris, Ovidrel), metabolism-endocrinology (Saizen, Serostim), neurology (Rebif), and dermatology (Raptiva). In the late 90s, Serono's management made the strategic decision to add small molecule drug discovery to their research portfolio, with the aim of mimicking and further extending the spectrum of action of the existing protein therapeutics with orally bioavailable next-generation products. As a hallmark of this new research paradigm, in late 1997, Serono acquired the GBRI (Glaxo Biomedical Research Institute), now SPRI (Serono Pharmaceutical Research Institute), located just outside Geneva, and during the following year therein established a new, state-of-the-art Chemistry Department, with the necessary manpower, expertise, as well as the medicinal, analytical, and combinatorial chemistry equipment, including extensive structure- and ligand-based design capabilities. In conjunction with a somewhat smaller Chemistry Department previously established at Serono's Boston-based research site SRBI (Serono Reproductive Biology Institute), Serono's chemists have now been working for around five years on a variety of small molecule drug discovery projects. As the first small molecules emerging from these efforts have started entering human clinical trials, the present article will give an account on some of the work performed to date.