The concept of a glucose-responsive insulin (GRI) has been a recent objective of diabetes technology. The idea behind the GRI is to create a therapeutic that modulates its potency, concentration or dosing relative to a patient's dynamic glucose concentration, thereby approximating aspects of a normally functioning pancreas. From the perspective of the medicinal chemist, the GRI is also important as a generalized model of a potentially new generation of therapeutics that adjust potency in response to a critical therapeutic marker. The aim of this Perspective is to highlight emerging concepts, including mathematical modelling and the molecular engineering of insulin itself and its potency, towards a viable GRI. We briefly outline some of the most important recent progress toward this goal and also provide a forward-looking viewpoint, which asks if there are new approaches that could spur innovation in this area as well as to encourage synthetic chemists and chemical engineers to address the challenges and promises offered by this therapeutic approach.
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The authors would like to acknowledge the Joint JDRF and Helmsley Charitable Trust sponsored Workshop on 'Design and Development of Glucose Responsive Insulins' held in New York, April 2016. The American Diabetes Association (ADA; 1-15-ACE-21) and the JDRF Diabetes Foundation (3-SRA-2015-117-Q-R; 2-SRA-2016-269-A-N); the Leona M. and Harry B. Helmsley Charitable trust (Award 2014PG-T1D002). All correspondence and requests for materials should be addressed to M.S.S.
The authors declare no competing financial interests.
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Bakh, N., Cortinas, A., Weiss, M. et al. Glucose-responsive insulin by molecular and physical design. Nature Chem 9, 937–944 (2017). https://doi.org/10.1038/nchem.2857
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