Elan Corporation, plc is a neuroscience-based biotechnology company that engages in the research, development, and commercial activities for neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, and autoimmune diseases, including multiple sclerosis and Crohn’s disease.
Dr. Zhao Ren is a Staff Scientist at Elan and leads a research team to develop robust biochemical and cellular assays that enable High Throughput Screening (HTS) and structure-activity relationship (SAR) studies. This research supports the small molecule drug discovery programs at Elan.
Dr. Ren received his M.D. from Sun Yat-sen University of Medical Sciences, Guangdong, China, and his Ph.D. in Molecular Pharmacology and Physiology from Brown University, where he studied glutamate receptor trafficking and its implications in learning and memory formation. He then completed a postdoctoral fellowship at Elan Pharmaceuticals, concentrating his research on a number of aspartate proteases involved in amyloid precursor protein processing. He revealed a novel molecular mechanism regulating the cleavage specificity of gamma secretase.
At Elan, the research team of Dr. Ren has established an extensive assay portfolio for many different therapeutic targets, including various kinases and proteases. The team uses a broad range of techniques, including PerkinElmer’s LANCE® TR-FRET and AlphaScreen®. In addition, they are also actively exploring the use of High Content Analysis (HCA) and label-free technologies for research and drug discovery. This work supports the development of disease-modifying therapies for neurodegenerative and autoimmune disorders.
Dr. Ren says, “Amongst all the technology platforms that we have evaluated and adopted over the past few years, PerkinElmer’s LANCE® TR-FRET and AlphaScreen® have quickly become the key drivers in accelerating our assay development effort. The sensitivity and versatility of both techniques enable rapid assay development, validation and expansion, while their homogenous nature is critical for HTS adaptation and miniaturization”.
As one example, AlphaScreen® technology has enabled the team to develop robust cellular assays to discover novel inhibitors of receptor tyrosine kinases (RTKs). These are an important class of drug targets due to their critical roles in cell proliferation and differentiation.
Dr. Ren says, “RTK inhibitors have been aggressively pursued in many different therapeutic areas, including oncology and inflammatory diseases. Homogeneous biochemical assays using recombinant kinase domains of RTKs have been widely adopted to drive inhibitor discovery and SAR studies. There is a lack of robust cellular assays that can measure RTK activity directly in a high throughput fashion. Recent advances in detection technologies, in particular the emergence of PerkinElmer’s AlphaScreen® platform, represent a major breakthrough in this frontier. These emerging technologies allow large-scale compound testing in a cellular context and are more conducive to the discovery of allosteric kinase inhibitors”.
“We adopted the AlphaScreen® technology and rapidly developed several robust cellular RTK assays measuring receptor autophosphorylation. Our AlphaScreen® assays showed excellent correlation with data generated from the conventional ELISA assays (Figure 1), but with marked improvement in assay throughput and HTS adaptability (Figures 2 and 3)”.
Figure 1: The AlphaScreen® assay demonstrates excellent correlation with potency data generated from a conventional ELISA assay utilizing the same antibody pair.
Figure 2: The AlphaScreen® assay shows robust signals and good tolerability to DMSO.
Figure 3: The AlphaScreen® assay shows an excellent Z’ that is sufficient for HTS.
“The high sensitivity of the AlphaScreen® assays enables efficient miniaturization (384 and 1536-well), and the homogeneous nature of these assays renders quick automation with liquid handlers and robotics. We have successfully implemented these assays for HTS and identified potent inhibitors for the respective RTK targets of interest. As for the future, we see many more opportunities where we can further harness the power of AlphaScreen® technology in support of our basic research and drug discovery efforts”.
To find out more about the research at Elan, please visit http://www.elan.com/.