Drug Discovery at AstraZeneca R&D Montréal

As a cornerstone of AstraZeneca PLC's vision to become the global leader in the overall therapeutic area of pain control, AstraZeneca R&D Montréal (AZRDM) focuses on the design, discovery and development of novel pharmaceutical agents that will provide innovative solutions to unmet medical needs in pain.

The Discovery Process at AZRDM

The approach at AZRDM is to fully integrate molecular biological, pharmacological and chemical technologies to develop candidate drugs for pain.

Step 1: Identifying and Validating Molecular Targets

The Analgesia Target Team identifies molecular targets, such as neurotransmitter receptors, enzymes and ion channels, that have a role in pain, particularly neuropathic pain. The team reviews the knowledge around mechanisms and molecules involved in causing or transmitting pain, and then selects targets that have the most convincing evidence that either blocking or activating the target with a drug will result in effective pain relief without side effects.

Step 2: Identifying and Optimizing a Lead Compound

The project team selects and implements one or more method (e.g. random screening, structure-based design) of finding chemical "hits", which are usually weak at the target but represent good starting points to create useful medicines. Based on the structure-activity relationship of the hit compounds at the target, our chemists create new compounds expected to have improved activity. The pharmacologists on the team help guide the synthesis by providing detailed characterization of each compound's potency and selectivity for the target, and on metabolic stability and pharmacokinetics for selected compounds. In repeated cycles of synthesis and testing, all relevant results are fed back to the chemists, so they can use it in their subsequent rounds of design and synthesis.

Step 3: Delivering a Candidate Drug

At the end of the Lead Compound optimization effort, AZRDM scientists recommend the nomination a candidate drug, based on a thorough evaluation of its efficacy, stability, bioavailability, kinetics, and most importantly, safety.

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