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Review
. 2022 Oct 27;13(11):1691-1698.
doi: 10.1021/acsmedchemlett.2c00375. eCollection 2022 Nov 10.

Advancing New Chemical Modalities into Clinical Studies

Maria-Jesus Blanco  1 , Kevin M Gardinier  2 , Mark N Namchuk  3
Affiliations
Review

Advancing New Chemical Modalities into Clinical Studies

Maria-Jesus Blanco et al. ACS Med Chem Lett. .

Abstract

Drug discovery and development has experienced an incredible paradigm shift in the past two decades. What once was considered a predominant R&D landscape of small molecules within a prescribed properties and mechanism space now includes an innovative wave of new chemical modalities. Scientists in the pharmaceutical industry can now strategize across a variety of modalities to find the best option to modulate a given target and provide treatment for a specific disease. We have witnessed a remarkable change not only in molecular design but also in creative approaches to drug delivery that have enabled advancement of novel modalities to clinical studies. In this Microperspective, we evaluate the critical differences between traditional small molecules and beyond rule of 5 compounds, peptides, oligonucleotides, and biologics for advancing into development, particularly their pharmacokinetic profiles and drug delivery strategies.

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Conflict of interest statement

The authors declare the following competing financial interest(s): M.N.N. discloses that his research is funded by AbbVie. He is a consultant for Axonis and on the SAB of Sionna Therapeutics.

Figures

Figure 1
Figure 1
Pie chart showing the percentage by modality of FDA-approved drugs in 2021–22.
Figure 2
Figure 2
Graphic summarizing the number of FDA-approved drugs by modality and route of administration for the past 2 years.
Figure 3
Figure 3
Representative approved drugs of different modalities in 2021–22.
Figure 4
Figure 4
Most common chemical modifications used in oligonucleotide drugs. B = nucleobase or nucleotide base substitution, including cytosine, guanine, adenine, and uracil.
See this image and copyright information in PMC

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