Sigma-Aldrich Corporation's innovative biological products and services business, Sigma Life Science has started a licensing programme aimed at contract research organizations (CROs) and pharmaceutical companies for its novel CompoZr Transporter Knockout Cell Lines for preclinical ADME screening and safety studies. Complete functional knockouts of transporters in the intestinal cell line (Caco-2) enables identification of critical safety and efficacy characteristics compared to current chemical inhibitor-based assays and more precise determination of a drug candidate's potential drug—drug interactions.

Cyprotex, a leading ADME-Tox service company with sites in both the UK and USA, is the first non-exclusive licensee in the programme.

The US Food and Drug Administration and the European Medicines Agency recently recommended defining a drug candidate's interactions with efflux transporters, which act as doorways for drugs to exit or be expelled from human cells, to ascertain a drug candidate's probable safety profile and potential for adverse drug—drug interactions. Current efflux transporter assays use standard chemical inhibitors that can interact with multiple transporters simultaneously. This may produce an ambiguous representation of a drug candidates true ADME properties in the human body or potential contradictions with other medications.

"Complete transporter knockout human cell lines identify efflux transporter interactions unambigously to produce a clearly defined safety profile for a drug candidate. Sigma's CRO and pharma licensing programme will facilitate rapid adoption of this superior approach to identifying potential safety issues and meeting the new regulatory guidelines," explains Paul Brooks, PhD., Market Segment Manager at Sigma Life Science.

The MDR1 (P-gp), BCRP and MRP2 Caco-2 single and double knockout cell lines were confirmed by genomic analysis and functional transporter activity assays. Sigma Life Science generated the cell lines using its CompoZr Zinc Finger Nuclease technology.

At the International Society for the Study of Xenobiotics' (ISSX) 18th North American Regional Meeting, new functional data on the gene knockout cell lines will be presented by Kathleen E Sampson, PhD, senior scientist at Sigma Life Science, during an industry sponsored symposia on October 16 and a poster session on October 17, 2012.

For continuing ADME studies in animals, Sprague-Dawley rats containing identical homozygous efflux transporter gene knockouts are also available for purchase from Sigma Advanced Genetic Engineering (SAGE) Labs.

Sigma Life Science is representing the Company's leadership in innovative biological products and services for the global life science market and offers an array of biologically-rich products and reagents that researchers use in scientific investigation.

Sigma-Aldrich is a leading Life Science and High Technology company whose biochemical, organic chemical products, kits and services are used in scientific research, including genomic and proteomic research, biotechnology, pharmaceutical development, the diagnosis of disease and as key components in pharmaceutical, diagnostics and high technology manufacturing.