Screening
References 1 Sandercock, AM et al. Identification of anti-tumour biologics using primary tumour models, 3-D phenotypic screening and image-based multi-parametric profiling. Molecular Cancer 2015; 14:147 2 Williams, G et al. Phenotypic screening reveals TNFR2 as a promising target for cancer immunotherapy. Oncotarget 2016; 7(42): 68278-91. 3 Salanti, A et al. Targeting human cancer by a glycosaminoglycan binding malaria protein. Cancer Cell 2015; 28(4):500-14. 4Turner, L et al. Severe malaria is associated with parasite binding to endothelial protein C receptor. Nature 2013; 498:502.
of label-free detection strategies for small molecules is currently under way.
In fewer than 10% of cases, high background binding of the phenotypic molecule to the host HEK293 cells will be observed. In all probability this is caused by high endogenous expression of the target which renders the molecule unsuitable for screening. This issue could potentially be addressed by optimising the technology for alter- native cell types.
Impact
cDNA expression cell microarrays now provide a very powerful approach for rapidly identifying the membrane targets of phenotypic molecules which has removed the traditional deconvolution bottle- neck from phenotypic drug discovery. Due to suc- cess rates which far surpass other methodologies, the approach has been widely adopted across the industry and has garnered considerable interest among academic
groups.The power of the technol- ogy to facilitate phenotypic drug discovery will only increase as libraries continue to expand and provide further coverage of the membrane pro- teome, incorporating both new membrane proteins as well as additional isoforms of proteins that are already represented.
As phenotypic drug discovery continues to advance, the accompanying target deconvolution efforts will undoubtedly expand our collective understanding of the critical receptors that are implicated in disease processes and that mediate the therapeutic response.
DDW
Dr Jim Freeth co-founded Retrogenix in 2008, developing a world-leading technology for identi- fying both the receptor targets and off-targets of antibodies, proteins, small molecules and viruses. Retrogenix now works with 14-15 top pharmaceu- tical companies, numerous drug discovery compa- nies and leading academics. Prior to Retrogenix, Jim spent more than 10 years in management with- in the biotech and pharmaceutical industry. A biol- ogist by training, Jim obtained his PhD at Manchester University, UK in 1997.
Dr Elizabeth Kingsley provides scientific support to the business development activities at Retrogenix, working closely with research groups at global pharmaceutical companies to plan pro- jects aiming to identify the specific cell surface tar- gets of biologics and small molecules. She also works more widely with biotechnology companies on PR communications and marketing strategies.
50 Drug Discovery World Fall 2017
Elizabeth has a PhD in molecular biology from the University of Manchester, UK.
Jo Soden co-founded Retrogenix and was instru- mental in developing and commercialising the cell microarray technology. Jo leads a talented team of scientists, overseeing all internal technology R&D activities and managing Retrogenix’s portfolio of commercial projects. She has contributed to numerous peer-reviewed scientific publications and her background includes 17 years of research experience at the University of Manchester, UK, where she also obtained her MPhil.
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