HIGH-THROUGHPUT DRUG discovery WITH THE EVOSEP ONE

Drug discovery is the process through which potential new medicines are identified. It involves a wide range of scientific disciplines, including biology, chemistry and pharmacology.

The complexity in drug development has increased manifolds over the past 40 years, requiring preclinical testing, investigational new drug applications, and completed clinical testing before marketing approval from the FDA.

Generally, new drug applications or biologics license applications are reviewed comprehensively before approval, and then drug performance is resubmitted to regulatory agencies for post-marketing studies. The overarching goal is to bring more efficient and safer treatments to the patients as quickly as possible after a thorough medical evaluation.

Covalent Protein Painting for Protein Structure Analysis and Drug Discovery in Cancer

Somatic DNA mutations derail gene expression and alter protein sequences, which contribute to tumorigenesis. However, the overall impact of somatic mutations on proteome-wide protein folding and protein-protein interactions during malignant transformation remains unknown.

We used covalent protein painting (CPP), a novel, high throughput mass spectrometric method to quantitatively measure alterations in protein structure and interaction. With CPP we screened more than 60 different cancer cell lines for aberrations in protein conformation. While many structural alterations of proteins were specific to a single cancer cell line, we identified a subset of structural alterations of proteins in the cancer conformational landscape that correlated with the growth inhibition profiles of drug candidates.

3D proteomic analysis with CPP in high sample throughput enables the discovery of cancer-associated structural alterations that may serve as biomarkers for malignant transformation and may provide leads for anti-cancer drug development.

Presenter: Casimir Bamberger, PhD (Research Associate at The Scripps Research Institute)

Label free ex-vivo organ specific identification of drug targets

Proteins are the primary targets of almost all small molecule drugs. However, even the most selectively designed drugs can potentially target number of unknown proteins. Identification of all potential drug targets can enable us to design better drugs and repurpose existing ones for different clinical diseases. Current state-of-the-art proteomics methodologies enable screening of 1000’s proteins against a small number of small molecules. However, higher throughput is required in order to determine protein targets of large number of drugs. Here I will present initial results on the development of a label free quantitative proteomics approach which enables screening of large number of small molecules against the proteome in a robust and rapid manner. I will demonstrate the applicability of this approach by identifying protein targets in rat organs ex-vivo.

Presenter: Tanveer S. Batth (Assistant Professor at The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen)