Tove Tuntland
Genomics Institute of Novartis Research Foundation (GNF), USA
Title: Target Based vs. Phenotypic Screening Approaches in Drug Discovery
Biography
Biography: Tove Tuntland
Abstract
Target-based drug discovery can effectively develop novel treatments for a validated target, but the process of target validation is complex and associated with high degree of uncertainty[1]. As an alternative to the target based approach, phenotypic screening is making a comeback in drug discovery. Such assays characterize phenotypic events related to disease modification and do not require prior understanding of the mechanism of action[2]. At GNF/Novartis, scientists have used both target based and phenotypic screening approaches to successfully identify novel drugs. Target based methods lead to the discovery of ceritinib (Zykadia™, formerly LDK378), a highly potent and selective anaplastic lymphoma kinase (ALK) inhibitor which was recently approved by the FDA for the treatment of patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) who were previously treated with crizotinib. Phenotypic screening led to the discovery of cipargamin (KAE609), the first new antimalarial drug candidate with a completely novel mechanism of action to reach phase 2 clinical development in over 20 years. When tested clinically in adults with uncomplicated P. vivax or P. falciparum malaria, cipargamin was shown to clear parasitemia after 3 days of repeated dosing. Also identified by phenotypic screening, the novel antimalarial drug KAF156 demonstrated activity against both liver and blood stage malaria, including artemisinin-resistant parasites. The approaches used to discover and develop the novel drugs ceritinib, cipargamin and KAF156 will be discussed.