A Small Molecule Renaissance? Teaching an Old Modality New Tricks

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New functionality for small molecule therapeutics can advance drug development.

By John Morrison, Ph.D., Bristol-Myers Squibb, and Steven Louie, Amgen

The pharmaceutical industry continues to evolve, developing strategies to take advantage of novel biological mechanistic discoveries and develop innovative new medicines. One approach has been molecular modality escalation into larger synthetic peptides and oligonucleotides, as well as biotechnology-derived proteins. These larger molecules often demonstrate good target engagement resulting in more prolonged or catalytic interactions as well as pharmacokinetic profiles more amenable to less frequent administration.1 However, these modalities are often unable to readily access intracellular targets across multiple tissue types, are generally not orally bioavailable, and are typically more complicated and expensive to prepare, process, purify, formulate, stabilize, and deliver.

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June 2018

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