Drug discovery: are productivity metrics inhibiting motivation and creativity?

Ullman, Fredrik; Boutellier, Roman

doi:10.1016/j.drudis.2008.06.015

Cited by 11 publications

(5 citation statements)

References 6 publications

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“…Current methods being applied to reduce cost and increase efficiency include outsourcing [15, 16], metrics [17, 18], and limiting the duration of a research project [19]. This is despite the obvious fact that drug discovery is a complex, highly interdisciplinary process [20] and inherently unpredictable [21, 22].…”

Section: Introductionmentioning

confidence: 99%

Advances in nuclear magnetic resonance for drug discovery

Powers

2009

Expert Opinion on Drug Discovery

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Background Drug discovery is a complex and unpredictable endeavor with a high failure rate. Current trends in the pharmaceutical industry have exasperated these challenges and are contributing to the dramatic decline in productivity observed over the last decade. The industrialization of science by forcing the drug discovery process to adhere to assembly-line protocols is imposing unnecessary restrictions, such as short project time-lines. Recent advances in nuclear magnetic resonance are responding to these self-imposed limitations and are providing opportunities to increase the success rate of drug discovery. Objective/Method A review of recent advancements in NMR technology that have the potential of significantly impacting and benefiting the drug discovery process will be presented. These include fast NMR data collection protocols and high-throughput protein structure determination, rapid protein-ligand co-structure determination, lead discovery using fragment-based NMR affinity screens, NMR metabolomics to monitor in vivo efficacy and toxicity for lead compounds, and the identification of new therapeutic targets through the functional annotation of proteins by FAST-NMR. Conclusion NMR is a critical component of the drug discovery process, where the versatility of the technique enables it to continually expand and evolve its role. NMR is expected to maintain this growth over the next decade with advancements in automation, speed of structure calculation, in-cell imaging techniques, and the expansion of NMR amenable targets.

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Section: Introductionmentioning

confidence: 99%

Advances in nuclear magnetic resonance for drug discovery

Powers

2009

Expert Opinion on Drug Discovery

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“…However, they are currently grappling with several challenges and tension. One of the primary challenges faced by big pharmaceutical companies is balancing the competing goals of efficiency and innovation [69]. Joint R&D could be a potential solution to address the challenges and tensions in drug discovery in large pharmaceutical enterprises [68].…”

Section: The Relationship Between Pharmaceutical Enterprises or Acade...mentioning

confidence: 99%

Forward or Backward: Lessons Learned from Small Molecule Drugs Approved by FDA from 2012 to 2022

Gu,

Sun,

You

et al. 2023

Molecules

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At every juncture in history, the design and identification of new drugs pose significant challenges. To gain valuable insights for future drug development, we conducted a detailed analysis of New Molecular Entitiy (NME) approved by the Food and Drug Administration (FDA) from 2012 to 2022 and focused on the analysis of first-in-class (FIC) small-molecules from a perspective of a medicinal chemist. We compared the change of numbers between all the FDA-approved NMEs and FIC, which could be more visual to analyze the changing trend of FIC. To get a more visual change of molecular physical properties, we computed the annual average trends in molecular weight for FIC across various therapeutic fields. Furthermore, we consolidated essential information into three comprehensive databases, which covered the indications, canonical SMILES, structural formula, research and development (R&D) institutions, molecular weight, calculated LogP (CLogP), and route of administration on all the small-molecule pharmaceutical. Through the analysis of the database of 11 years of approvals, we forecast the development trend of NME approval in the future.

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“…Other ill-conceived managerial decisions have also contributed to the decline in the productivity and creativity of the pharmaceutical industry, which include outsourcing, , the application of metrics, , and restricting project timelines . In effect, drug discovery is being treated like any other manufacturing process where cost savings is driving business decisions, but assembly line science does not work because the process is highly interdisciplinary and unpredictable. , Outsourcing simply leads to the isolation of critical components of the process, but breakthroughs and problem-solving require routine interactions between experts with diverse skill sets and experiences.…”

Section: Drug Discovery Challengesmentioning

confidence: 99%

The Current State of Drug Discovery and a Potential Role for NMR Metabolomics

Powers

2014

J. Med. Chem.

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The pharmaceutical industry has significantly contributed to improving human health. Drugs have been attributed to both increasing life expectancy and decreasing health care costs. Unfortunately, there has been a recent decline in the creativity and productivity of the pharmaceutical industry. This is a complex issue with many contributing factors resulting from the numerous mergers, increase in out-sourcing, and the heavy dependency on high-throughput screening (HTS). While a simple solution to such a complex problem is unrealistic and highly unlikely, the inclusion of metabolomics as a routine component of the drug discovery process may provide some solutions to these problems. Specifically, as the binding affinity of a chemical lead is evolved during the iterative structure-based drug design process, metabolomics can provide feedback on the selectivity and the in vivo mechanism of action. Similarly, metabolomics can be used to evaluate and validate HTS leads. In effect, metabolomics can be used to eliminate compounds with potential efficacy and side effect problems while prioritizing well-behaved leads with druglike characteristics.

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Drug discovery: are productivity metrics inhibiting motivation and creativity?

Cited by 11 publications

References 6 publications

Advances in nuclear magnetic resonance for drug discovery

Advances in nuclear magnetic resonance for drug discovery

Forward or Backward: Lessons Learned from Small Molecule Drugs Approved by FDA from 2012 to 2022

The Current State of Drug Discovery and a Potential Role for NMR Metabolomics

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