Outsourcing drug target proteins and high-throughput screening

Early stages of drug discovery efforts are dependent on the identification and production of high-quality drug target proteins, the rapid screening of compound libraries against these targets, and the generation of preliminary absorption, distribution, metabolism, and excretion (ADME) and toxicology data for the lead compounds. Alex Vodenlich reports.

Genomics efforts have flooded drug discovery with potential new drug targets and new parallel combinatorial synthesis methods are providing more compounds that must be screened for activity. The tremendous challenge facing the high-throughput screening (HTS) scientists today is to screen more compounds against more targets. Identification of new lead compounds must become more efficient by using faster and more quantitative screening methods. Assay automation, to increase the speed of reagent handling, and miniaturisation, to decrease reagent costs and consumption of compound libraries, are critical success factors.

Drug companies now receive timely, confidential, robust and customised products from suppliers that significantly impact the early phase of new drug discovery. Outsourcing services purify recombinant proteins according to customer specifications, assist investigators with protein optimisation, screening, characterisation and assay applications. To make this type of collaboration successful, companies like PanVera Corporation must supply unique products, such as protein targets, HTS assay reagents, and drug metabolising enzymes and assays, use standardised scientific procedures, comprehensive documentation, and continuous two-way project feedback. Investigators receive ongoing access to new discovery technologies as part of their outsourcing experience.

Discovery strategies

PanVera offers discovery outsourcing services. Its technology platforms combine the expression, purification, and biochemical characterisation of recombinant human proteins and their incorporation into non-radioactive drug screening assays. These activities are carried out both as part of proprietary product development activities and as contract services for pharmaceutical, genomics, and biotechnology clients. Development and production services include cloning and molecular biology, expression optimisation, purification, and biochemical/functional characterisation of proteins. PanVera's bacterial and insect cell expression systems have produced hundreds of proteins under contract for large pharmaceutical and genomics companies.

PanVera's manufacturing systems allow for the expression of milligram to gram quantities of proteins using strict standardised methods to ensure consistency and reliability. PanVera also offers custom assay development and reagent production services. PanVera provides a regulated manufacturing environment to assure project integrity balanced with the responsiveness and adaptability of a focused services enterprise. PanVera project managers are in continual communication with its clients, assuring flexibility and accountability during the project.

PanVera has introduced large numbers of recombinant human protein targets of broad interest, including steroid hormone receptors, signal transduction proteins and drug metabolising enzymes. Recognising the demands of target screening, PanVera established itself as a leader in the use of fluorescence polarisation (FP). PanVera clients have found fluorescent methods to be a primary detection format in HTS. FP now approaches the sensitivity of radioactive techniques and is amenable to miniaturisation and homogeneous formats that eliminate wash steps, multiple incubations, and separations. FP technologies have gained acceptance as a preferred method in HTS, especially for protein-protein or protein-DNA interactions.

Proteins and reagents are sized forbench-scale experiments, as well as in bulk for HTS and protein structure studies. Products are custom dispensed, lot controlled, packaged, and delivered globally according to the client's specifications. This approach insures the reliable supply of robust and competitively priced assays reagents. PanVera's success in winning repeat sourcing agreements from the world's most exacting scientists is evidence of its client-centric process. For a decade, PanVera has built its reputation for being a proven technical resource to HTS groups while providing drug discovery investigators the opportunity to expand existing development and production capacity quickly without an increase in staff and/or facilities.

Conclusion

The dynamics of discovering and developing new pharmaceutical and healthcare products are continually influenced by changes in technologies, regulatory environments, and financial considerations. Outsourcing, as a strategic resource, is becoming more popular. World-class discovery partners are available to accelerate client investigations, providing confidential and certain results. u

ENQUIRY No 25

Alex Vodenlich is with PanVera Corporation,Madison, WI, USA. www.panvera.com

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