Oncology and Immuno-Oncology Precision Medicines:
From Hit-Finding to Pre-Clinical Candidate Selection

Discovery of precision medicines requires the identification of potent and original hits with a robust validation of their mechanisms of action at the molecular level. The discovery of Naa50 binders/inhibitors using DNA-encoded (DEL) illustrates this challenge:

Two novel compounds were identified as Naa50 binders/inhibitors using DNA-encoded (DEL) technology. Biophysical and biochemical data as well as cocrystal structures were obtained for both compounds (3a and 4a) to understand their mechanism of action. These data were also used to rationalize the binding affinity differences observed between the two compounds and a MLGP peptide-containing substrate. Cellular target engagement experiments further confirm the Naa50 binding of 4a and demonstrate its selectivity toward related enzymes (Naa10 and Naa60). Additional analogs of inhibitor 4a were also evaluated to study the binding mode observed in the cocrystal structures.

In this webinar, the Hitgen talk will focus on the application of DNA-encoded library (DEL) technology: the mechanics of DEL, the advantages and challenges of the technology to those considering DEL technology for identifying ligands for their target of interest.

Going one step further, the use of patient-derived xenograft (PDX) enables translation of in vitro results into relevant in vivo predictive pharmacological models to human.

Much progress has been made in understanding the mechanisms of cancer and in the development of innovative therapeutic agents. Despite this, the attrition rates between target discovery and drug marketing approval remains high, especially in oncology. It is hypothesized that one of the main reasons underlying these undesirable statistics is believed to be the lack of predictive power of the model systems used in the preclinical setting. Tumor heterogeneity is a challenge in cancer research and drug development, and it is now demonstrated that patient-derived xenograft (PDX) cancer models should clearly help to better mimic the situation of human cancer pathologies.

The Oncodesign talk will focus on how patient-derived xenograft (PDX) and PDX-derived models should be incorporated into different stages of the drug discovery process, taking the example of Drug Positioning in Breast Cancer with relevant human projection.

Join Oncodesign and HitGen across selected examples, studying the paradigm of novel approaches in the discovery of new drugs in Oncology. It will be a unique opportunity to interactively discuss, debate and answer questions about how oncology drug discovery works today, and how to better apply the concept of personalized medicine to your oncology research within a consortium of experts in their own field from hit finding to pharmacology.

Register for this webinar to gain deeper insight into DRIVE-SM (DRug Integrative discovery for small molecule) premium Integrated Drug Discovery Services.