Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Med Chem. 2011 Oct 13;54(19):6771-85. doi: 10.1021/jm200666a. Epub 2011 Sep 14.

Chemical structural novelty: on-targets and off-targets.

Author information

  • 1University of California, San Francisco, Department of Bioengineering and Therapeutic Sciences, Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94158, United States.

Abstract

Drug structures may be quantitatively compared based on 2D topological structural considerations and based on 3D characteristics directly related to binding. A framework for combining multiple similarity computations is presented along with its systematic application to 358 drugs with overlapping pharmacology. Given a new molecule along with a set of molecules sharing some biological effect, a single score based on comparison to the known set is produced, reflecting either 2D similarity, 3D similarity, or their combination. For prediction of primary targets, the benefit of 3D over 2D was relatively small, but for prediction of off-targets, the added benefit was large. In addition to assessing prediction, the relationship between chemical similarity and pharmacological novelty was studied. Drug pairs that shared high 3D similarity but low 2D similarity (i.e., a novel scaffold) were shown to be much more likely to exhibit pharmacologically relevant differences in terms of specific protein target modulation.

PMID:
21916467
[PubMed - indexed for MEDLINE]
PMCID:
PMC3188662
Free PMC Article

Images from this publication.See all images (13)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
Figure 13
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society Icon for PubMed Central
    Loading ...
    Write to the Help Desk