Drug screening Novartis

To demonstrate the utility of optophoresis in the preclinical stages of drug discovery, we screened several cell lines for their response to three standard chemotherapy drugs flu-darabine, vincristine, and Gleevec (imatinib mesylate, Novartis Pharmaceuticals, Basel, Switzerland) (Figure 7.6). To perform these measurements with the fast-scan technique, cells were suspended in a 9-mm-diameter well in a sample holder. The bottom surface of... 

Jacoby E,Schuffenhauer A, Popov M, etal. (2005) Key aspects of the Novartis compound collection enhancement project for the compilation of a comprehensive chemogenomics drug discovery screening collection. Curr. Top. Med. Cfcem. 5 397-411. 

Chapter 1 contributed from the Novartis Molecular and Library Informatics group focuses on small molecules for chemogenomics based drug discovery and summarizes the main compound categories and selection methods of relevance for the compilation of a comprehensive discovery screening collection. 

In an effort to interfere with CML progression, pharmaceutical scientists at Novartis first cloned and produced recombinant B CR-AB L kinase. With the availability of this enzyme in sufficient quantity and purity, a mass in vitro screen of a series of enzyme inhibitors was implemented to identify drug candidates that produce an optimum pharmaceutical profile. From these, they identified STI571 (Gleevec) as a lead candidate to block the kinase activity of BCR-ABL. STI571 acts as a competitive inhibitor of ATP binding to the enzyme, which leads to the inhibition of tyrosine phosphorylation of proteins involved in BCR-ABL signal transduction [39,40]. 

A library of about 7000 natural SMs from Novartis and the Natural Product Collaborative Drug Discovery Group was screened in an attempt to discover an inhibitor of Tcf/p-catenin interaction, implicated in colorectal and other cancer types. Six potent inhibitors of microbial origin were identified and suggested for further structural refinement for cancer therapy. However, an additional screen of approximately 45,000 synthetic compounds from the Novartis collection yielded no additional inhibitors of this interaction [22]. 

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