PROTACs with linkers optimised to improve physical properties. Replacement of the PEG linker in 82 with piperazine and pyrimidine moieties (alongside other changes) greatly reduced lipophilicity and metabolic clearance of 83. Chessum et al. [126], developed pirin-targeting probe 84 in only three focused design iterations (through 85 and 86) by seeking to optimise physical properties instead of potency
All authors contributed to the conception and organisation of this review. RT prepared the first draft of the manuscript, and all authors contributed to the writing and development of additional sections. All authors contributed to manuscript revision and approved the submitted version.
The authors declare that they have no conflicts of interest.
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This work was supported by AstraZeneca with a CASE award, and the EPSRC with a CASE Conversion grant (EP/R513325/1). AstraZeneca approved the final submitted version of the manuscript. The industrial supervisor/author (CF), together with the other authors, contributed to the design, writing, proof-reading and submission of this review.
© The Author(s) 2020.