Monrovia, California (PressExposure) May 07, 2013 -- Maureen Beresini, Senior Scientist at Genentech, will present on "From HTS to Mechanism: Kinase Screening Strategies That Maximize Hit Value" at the 8th Protein Kinases in Drug Discovery Conference on July 8-9, 2013 in Boston.
In recent years, kinase screening has evolved to address our growing understanding of kinase signaling, activation states, and resistance mechanisms. Pre-clinical and clinical data have illustrated that kinase inhibitors can allosterically activate or inhibit signaling, revealed mechanisms of resistance to targeted inhibitors, and importantly, demonstrated that differential binding modes can lead to vastly different functional effects. These data have influenced the way we do drug discovery, and in effect, the way we conduct HTS campaigns. Maureen Beresini's team devise screening strategies unique to each kinase. A solid understanding of the kinase and a clearly defined target candidate profile are used to develop a well-targeted primary screening assay and a suite of follow-up assays that efficiently characterize primary hits and identify those with desired modes of action. Maureen Beresini's presentation will describe three critical avenues for maximizing HTS hit value: 1). Minimizing detection interference 2). Minimizing nonspecific inhibition 3). Maximizing fit to desired mechanism of action. Examples will be used to illustrate how primary screens coupled with information-rich IC50 evaluations have been used to direct hit triage efforts towards the most favorable compounds.
Maureen Beresini has over 20 years of experience in small molecule drug discovery at Genentech. She leads a group that develops and provides biochemical and cellular assays to promote the discovery of small molecule therapeutics. In recent years, Maureen has focused on high-throughput screening. In addition to the assays, she has contributed to the establishment of high-throughput automated systems and processes for conducting assays and managing compounds.
To remain competitive in the kinase field, stay abreast with recent development trends and technological advancements aimed towards challenges which accompany the development of ATP-competitive kinase inhibitors and problems of gatekeeper-associated drug resistance. GTC's 8th Protein Kinases in Drug Discovery Conference will provide an overview of the preclinical development of kinase inhibitors for cancers and inflammatory diseases. Key highlights include discussions on how phenotypic screening can be used for the identification of novel kinase targets and profiling, challenges and limitations of phenotypic screening, the use of physiologically relevant assays, structure-based drug design and cheminformatics tools, as well as strategies to develop selective inhibitors by targeting target inactive and active (DFG-out/in) kinases.