Next Article in Journal
Template Effect of the Graphene Moiré Lattice on Phthalocyanine Assembly
Next Article in Special Issue
Synthesis and Evaluation of Novel 2-Pyrrolidone-Fused (2-Oxoindolin-3-ylidene)methylpyrrole Derivatives as Potential Multi-Target Tyrosine Kinase Receptor Inhibitors
Previous Article in Journal
Acetylcholinesterase Inhibitory Meroterpenoid from a Mangrove Endophytic Fungus Aspergillus sp. 16-5c
Previous Article in Special Issue
Discovery and Biological Evaluation of a Series of Pyrrolo[2,3-b]pyrazines as Novel FGFR Inhibitors
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessArticle
Molecules 2017, 22(5), 730; doi:10.3390/molecules22050730

Assessing Scaffold Diversity of Kinase Inhibitors Using Alternative Scaffold Concepts and Estimating the Scaffold Hopping Potential for Different Kinases

Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Dahlmannstr. 2, Bonn D-53113, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Pierre Koch and Stefan Laufer
Received: 13 April 2017 / Revised: 26 April 2017 / Accepted: 1 May 2017 / Published: 3 May 2017
(This article belongs to the Special Issue Kinase Inhibitors)
View Full-Text   |   Download PDF [1141 KB, uploaded 3 May 2017]   |  

Abstract

Publicly available kinase inhibitors provide a large source of information for structure–activity relationship analysis and kinase drug design. In this study, publicly available inhibitors of the human kinome were collected and analog series formed by kinase inhibitors systematically identified. Then, alternative scaffold concepts were applied to assess diversity and promiscuity of kinase inhibitors. Over the past two years, the number of publicly available kinase inhibitors with high-confidence activity data more than doubled, but coverage of the human kinome only slightly increased. Approximately 70% of current kinase inhibitors belonged to analog series. However, the detectable degree of promiscuity among these kinase inhibitors remained low. Approximately 76% of all inhibitors were only annotated with a single kinase, compared to ~70% two years ago. For many kinases, the assessment of scaffold diversity among their inhibitors and the distribution of differently defined scaffolds over analog series made it possible to assess scaffold hopping potential. Our analysis revealed that the consideration of conventional compound-based scaffolds most likely leads to an overestimation of scaffold hopping frequency, at least for compounds forming analog series. View Full-Text
Keywords: kinase inhibitors; analog series; compound-based scaffolds; analog series-based scaffolds; structural diversity; promiscuity; scaffold hopping kinase inhibitors; analog series; compound-based scaffolds; analog series-based scaffolds; structural diversity; promiscuity; scaffold hopping
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Dimova, D.; Bajorath, J. Assessing Scaffold Diversity of Kinase Inhibitors Using Alternative Scaffold Concepts and Estimating the Scaffold Hopping Potential for Different Kinases. Molecules 2017, 22, 730.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top