Alan Palkowitz wants to diversify Lilly's discovery strategy Credit: Eli Lilly

Eli Lilly has activated a new web-based tool for lab researchers to submit compounds for testing in four disease areas: Alzheimer's disease, angiogenesis, diabetes and osteoporosis. The Indianapolis-based pharma hopes this free initiative, called Phenotypic Drug Discovery (PD2), will generate novel leads that could form the basis of future collaborations and licensing agreements. Contributing researchers, or their institutions, will maintain all rights to the submitted compounds, whereas Lilly gets first rights to negotiate a collaboration or licensing agreement. Molecules that make it through an initial set of criteria undergo a series of assays to determine biological activity in each of the four disease areas. This is followed by secondary assays designed to probe the biological mechanism. In angiogenesis, for instance, a secondary assay determines whether the compound influences any kinase signaling pathway. Results from these tests are compared to standard compounds, which act as positive controls. New entities that differentiate themselves from those controls, either through unique structures or biochemical mechanisms, would be candidates for licensing or a collaboration agreement, says Alan Palkowitz, Lilly's vice president of discovery chemistry. Researchers receive in-depth reports of the results from each disease module, and can use or publish that data in any way they choose, regardless of the outcome of negotiations. The emphasis on phenotypic assays is an extension of Lilly's own internal program, “We're really trying to maximize that investment [in phenotypic assays],” says Palkowitz. Phenotypic assays can reveal activities that may be missed with target-based assays, he adds. That's especially true with academic compounds that are often based on natural products and may have broad-spectrum activities. “I think the standard fluorescence-based high-throughput screen is not as meaningful for our compounds,” says Peter Wipf, professor of chemistry and pharmaceutical sciences at the University of Pittsburgh, Pennsylvania, who consulted with Lilly during the design and development of PD2. PD2 has good potential to jumpstart research, says Lesa Mitchell, vice president with the Ewing Marion Kauffman Foundation in Kansas City, Missouri, which focuses on entrepreneurship and has its own iBridge Network designed to provide web-based information on early-stage academic research for entrepreneurs, industry representatives, and academics to access. “The more we see sharing of compounds, the more we're going to advance commercialization,” says Mitchell. She is also impressed by Lilly's commitment as evidenced by presentations and outreach. “[They are] really taking this seriously.”