Whole cell screening is used as an effective, rapid and sensitive method to identify novel pharmacophores with biological activity from our natural product extract collection. Selectivity of compounds can be quickly discerned with in vitro testing across a panel of oncology and anti-infective assays. For our initial anti-infective screens, we assay against key clinically relevant pathogens: Staphyloccus aureus, Escherichia coli, and Candida albicans. On the oncology side, we employ a drug resistant human colon tumor cell line (HT29) and a sensitive murine melanoma cell line (B16) to screen for novel oncolytic agents.

Primary Screening Paradigm

Compounds identified with anti-infective activity are further evaluated against a panel of secondary assays to quickly discern selectivity and pathogen sensitivity. For anti-bacterial agents, we include both drug susceptible as well as drug resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), Penicillin-resistant Streptococcus pneumoniae (PRSP), and Vancomycin-resistant Enterococcus faecium (VRE). In addition, we screen against pathogens such as Haemophilus influenzae and Streptococcus pneumoniae which are critical to assess therapeutic potential of the agent in community acquired pneumonia. Similarly, we include other clinically relevant species of fungi in the secondary panel including Candida glabrata, Candida krusei, Candida tropicalis, Candida parapsilosis as well as Aspergillus fumigatus. Together, these organisms account for more than 90% of fungal infections.

Agents identified with putative anti-cancer activity are tested against a more extended panel of human tumor cell lines, including breast adenocarcinoma (MDA-MB-231), prostate adenocarcinoma (PC-3), non-small cell lung cancer (NCI-H292) and a multi-drug resistant ovarian cancer cell line (OVCAR-3). In addition, the growth inhibitory activity of the identified anti-cancer agents against normal skin fibroblasts (CCD-27sk) is analyzed. Such in vitro characterization allows Nereus to rapidly assess the potential therapeutic selectivity of these compounds.