Challenges and Opportunities in the Synthesis of Antibody Drug Conjugate Payloads
Jeremy Parker, Project Leader, AstraZeneca
Payloads for Antibody Drug Conjugates are typically highly complex
molecules based on natural products, the preparation of which involves long and
complex multi-step synthesies. Process Chemistry is focussed on
introducing new, more efficient routes (Route Design) and better, higher
yielding steps (Process Design). These activities can be applied to the
preparation of Antibody Drug Conjugate Payloads, significantly reducing
delivery times and campaign costs, as well as reducing the number steps that need
to be performed in expensive high containment facilities. The high synthetic
complexity of Antibody Drug Conjugate Payloads also drives the desire to
identify alternative, simpler molecules. The use of principal component
analysis to analyse known lists of available cytotoxic molecules has the
opportunity to promote the use of payloads that target alternative
chemotherapeutic mechanisms as well as identifying those which are structurally
simple and/or commercially available.
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