A practical view of 'druggability'.

@article{Keller2006APV,
  title={A practical view of 'druggability'.},
  author={Thomas H. Keller and Arkadius Pichota and Zheng Yin},
  journal={Current opinion in chemical biology},
  year={2006},
  volume={10 4},
  pages={
          357-61
        }
}

Figures from this paper

Integrated Teaching of Structure-Based Drug Design and Biopharmaceutics: A Computer-Based Approach.
TLDR
An educational approach using a case study is described in which students “design” a potential drug through use of software, most of which is Web-based and freely available.
Medicinal chemistry for 2020.
TLDR
The future of medicinal chemistry and the educational preparation that will be required for future medicinal chemists are considered and the five main angles to be addressed are: protein-protein interactions; peptides and peptidomimetics; molecular diversity and pharmacological space; molecular pharmacodynamics; and early-stage clinical efficacy and safety.
Multi-target pharmacology: possibilities and limitations of the “skeleton key approach” from a medicinal chemist perspective
  • A. Talevi
  • Biology, Chemistry
    Front. Pharmacol.
  • 2015
TLDR
Computational strategies to approach the identification of novel multi-target agents are overviewed and challenging restrictions on the topology or flexibility of the candidate drugs are briefly discussed.
Evaluation of blockbuster drugs under the rule-of-five.
TLDR
The current drug research techniques, combinatorial synthesis and high throughput screening, enabled the obtaining and pre-evaluation of thousands of compounds in short time, and Lipinski's Rule-of-five is concluded to be very useful to select better compounds in chemolibraries, but it must be used carefully and with criteria, to avoid a possible exclusion of promising compounds.
Druggability Assessment of Allosteric Proteins by Dynamics Simulations in the Presence of Probe Molecules
TLDR
A new methodology that successfully predicts the druggability and maximal binding affinity for a series of challenging targets, including those that function through allosteric mechanisms, and provides insights into novel druggable sites and the target’s structural changes that would accommodate, if not promote and stabilize, drug binding.
An overview of molecular hybrids in drug discovery
  • G. Bérubé
  • Biology, Chemistry
    Expert opinion on drug discovery
  • 2016
TLDR
This review covers the main research published between early 2013 to mid-2015 and takes into account several previous reviews on the subject, with particular attention given to anticancer hybrids.
Structure-based Ligand Design and the Promise Held for Antiprotozoan Drug Discovery*
  • W. Hunter
  • Biology, Chemistry
    Journal of Biological Chemistry
  • 2009
TLDR
Current strategies and benefits of a structure-based approach to support early stage drug discovery will be described and new approaches to support discovery of antiparasitic compounds promise much.
The emerging field of chemo‐ and pharmacoproteomics
  • S. Hess
  • Biology, Chemistry
    Proteomics. Clinical applications
  • 2013
TLDR
Chemo‐ and pharmacoproteomics has already contributed significantly to the identification of novel drug targets and their mechanisms of action(s) and this interdisciplinary approach will likely be used more broadly in the future.
...
...

References

SHOWING 1-10 OF 51 REFERENCES
Drug research: myths, hype and reality
  • H. Kubinyi
  • Chemistry, Biology
    Nature Reviews Drug Discovery
  • 2003
TLDR
The search for new drugs, especially in lead optimization, is an evolutionary process that is only likely to be successful if new methods merge with classical medicinal chemistry knowledge, and new methods must be as good as the medicinal chemistry they are based on.
A comparison of physiochemical property profiles of development and marketed oral drugs.
TLDR
A study in which the distributions of physiochemical properties of oral drugs in different phases of clinical development are compared to those already marketed, showing that the mean molecular weight of orally administered drugs in development decreases on passing through each of the different clinical phases and gradually converges toward the mean Molecular weight of marketed oral drugs.
Molecular properties that influence oral drug-like behavior.
TLDR
This review will demonstrate how trends in simple properties of the data can be used prospectively to compare and prioritize groups of compounds, chemical libraries and different chemical series with greater reliability than for predicting drug-likeness of single compounds.
Effects of Conformational Dynamics on Predicted Protein Druggability
TLDR
To investigate the influence of a protein’s conformational flexibility on its druggability assessment, MD simulations on three proteins are reported, and how inherent receptor flexibility and the accompanying dynamic fluctuations influence predicted pocket Druggability is investigated.
Characteristic physical properties and structural fragments of marketed oral drugs.
TLDR
Oral drugs tend to be lighter and have fewer H-bond donors, acceptors, and rotatable bonds than drugs with other routes of administration, and it is demonstrated that the mean property values for oral drugs do not vary substantially with respect to launch date, suggesting that the range of acceptable oral properties is independent of synthetic complexity or targeted receptor.
Nonleadlikeness and leadlikeness in biochemical screening.
  • G. Rishton
  • Biology, Chemistry
    Drug discovery today
  • 2003
Lead- and drug-like compounds: the rule-of-five revolution.
  • C. Lipinski
  • Chemistry, Biology
    Drug discovery today. Technologies
  • 2004
Navigating chemical space for biology and medicine
Despite over a century of applying organic synthesis to the search for drugs, we are still far from even a cursory examination of the vast number of possible small molecules that could be created.
Characterization of protein-ligand interaction sites using experimental and computational methods.
TLDR
Current progress in experimental and computational methods for identifying and characterizing druggable ligand binding sites on protein targets is reviewed, including a discussion of successful nuclear magnetic resonance, X-ray crystallography and tethering technologies.
...
...