Format

Send to

Choose Destination
See comment in PubMed Commons below
Bioorg Med Chem Lett. 2012 Mar 15;22(6):2242-6. doi: 10.1016/j.bmcl.2012.01.095. Epub 2012 Feb 1.

Antidotes to anthrax lethal factor intoxication. Part 3: Evaluation of core structures and further modifications to the C2-side chain.

Author information

1
PanThera Biopharma, LLC, Aiea, HI 96701, USA.

Abstract

Four core structures capable of providing sub-nanomolar inhibitors of anthrax lethal factor (LF) were evaluated by comparing the potential for toxicity, physicochemical properties, in vitro ADME profiles, and relative efficacy in a rat lethal toxin (LT) model of LF intoxication. Poor efficacy in the rat LT model exhibited by the phenoxyacetic acid series (3) correlated with low rat microsome and plasma stability. Specific molecular interactions contributing to the high affinity of inhibitors with a secondary amine in the C2-side chain were revealed by X-ray crystallography.

PMID:
22342144
PMCID:
PMC3295836
DOI:
10.1016/j.bmcl.2012.01.095
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center