The Laboratory of Synthetic Chemistry (LSC) has been established with a primary preclinical objective to provide chemistry support to the cancer drug discovery and development efforts of the Developmental Therapeutics Program and the projects approved by the Joint Development Committee of DCTD-CCR (JDC). Towards this end LSC will focus its activities on lead optimization, an essential and integral part of new drug discovery and development. Novel synthetic methodologies will be developed to create new analogs based on the effective lead compounds to improve pharmaceutical profiles by addressing the following drug properties: activity, tumor selectivity, solubility, bioavailability, stability and ADME/PK in an iterative fashion. The laboratory is engaged in developing new relevant synthesis methodologies for applications by the wider extramural community, especially those funded by DCTD. Most recently, DCTD in conjunction with the Center for Cancer Research and the Office of the Director, NCI established a new program called the Chemical Biology Consortium (CBC) to facilitate the discovery and development of new agents to treat cancer. The CBC is expected to be an integrated research consortium at the cutting edge of chemical biology and molecular oncology that will work with various programs within NCI and outside scientific community, establish an iterative cancer drug discovery group on the scale of a small biotechnology concern, and advance new cancer therapy into the clinic. The goal of the CBC is to focus on unmet therapeutic needs in oncology that are not currently addressed by the private sector, including the pharmaceutical industry. To address this challenge and to re-establish NCI as a major player in the national cancer therapeutic arena, successful interaction of CBC Screening and Chemistry centers and other scientific groups is necessary. To achieve this goal, the LSC has become the CBC Chemistry support center that will interact with various DCTD centers and programs within NCI and outside contractor laboratories to facilitate the identification of new drug discoveries through medicinal chemistry with the ultimate goal of developing new clinical candidates.