Structural Approach to Assessing the Innovativeness of New Drugs Finds Accelerating Rate of Innovation

ACS Medicinal Chemistry Letters
Todd J Wills, Alan H Lipkus

Abstract

Measuring innovation in the pharmaceutical industry is challenging. Counts of new molecular entities (NMEs) approved by the Food and Drug Administration (FDA) are commonly used, but this measure only gauges quantity not innovativeness. A new indicator of innovation for small molecule and peptide drugs based on structural novelty is proposed and used to analyze recent trends in pharmaceutical innovation. We show pharmaceutical innovation has significantly increased over the last several decades despite recent concerns over an innovation crisis and find Pioneers (a NME whose shape and scaffold were not used in any previously FDA-approved drugs) are significantly more likely to be the source of promising new therapies. Analysis of the underlying source of structural innovation indicates that scaffolds first reported in the CAS REGISTRY five or less years prior to their Investigational New Drug application (IND) or on scaffolds populated with 50 or less other compounds at the time of IND tend to be the main source of Pioneers. Our analysis also shows a widening structural innovation gap between large pharmaceutical companies (Big Pharma) and the rest of the ecosystem even though the number of Big Pharma originated Pioneers has incr...Continue Reading

References

Jul 19, 1996·Journal of Medicinal Chemistry·G W Bemis, M A Murcko
Dec 2, 2009·Nature Reviews. Drug Discovery·Bernard Munos
May 18, 2013·Nature Reviews. Drug Discovery·Aaron S Kesselheim, Jerry Avorn
Jun 1, 2013·Clinical Pharmacology and Therapeutics·A S KesselheimJ Avorn
Jan 30, 2014·Journal of Medicinal Chemistry·Richard D TaylorAlastair D G Lawson
Oct 20, 2015·Drug Discovery Today·Ajay Gautam, Xiaogang Pan
Oct 27, 2015·BMJ : British Medical Journal·Huseyin NaciElias Mossialos
Feb 4, 2016·Journal of Medicinal Chemistry·Ye HuJürgen Bajorath
May 12, 2017·Current Opinion in Chemical Biology·Ruiwu LiuKit S Lam
May 22, 2018·Trends in Pharmacological Sciences·Misty M AttwoodHelgi B Schiöth
Oct 12, 2019·The Journal of Organic Chemistry·Alan H LipkusTodd J Wills
Feb 6, 2020·Nature Reviews. Drug Discovery·Asher Mullard
Apr 18, 2020·Nature Reviews. Drug Discovery·Michael S RingelUlrik Schulze

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Citations

Apr 3, 2021·Bioorganic & Medicinal Chemistry Letters·Lewis D Pennington, Ingo Muegge
Apr 19, 2021·Briefings in Bioinformatics·Jianbo FuFeng Zhu
May 14, 2021·Journal of Medicinal Chemistry·Paul D LeesonAndrew R Leach

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Methods Mentioned

BETA
in-silico methods

Software Mentioned

AdisInsight
CAS
CAS REGISTRY
Big

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