Radiolabelling and positron emission tomography of PT70, a time-dependent inhibitor of InhA, the Mycobacterium tuberculosis enoyl-ACP reductase.

Authors :: Wang H
Liu L
Lu Y
Pan P
Hooker JM
Fowler JS
Tonge PJ
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2015 Nov 01; Vol. 25 (21), pp. 4782-4786. Date of Electronic Publication: 2015 Jul 14.
Publication Year :: 2015
Abstract: PT70 is a diaryl ether inhibitor of InhA, the enoyl-ACP reductase in the Mycobacterium tuberculosis fatty acid biosynthesis pathway. It has a residence time of 24 min on the target, and also shows antibacterial activity in a mouse model of tuberculosis infection. Due to the interest in studying target tissue pharmacokinetics of PT70, we developed a method to radiolabel PT70 with carbon-11 and have studied its pharmacokinetics in mice and baboons using positron emission tomography.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Subjects :: Animals
Anti-Bacterial Agents chemistry
Anti-Bacterial Agents pharmacokinetics
Antirheumatic Agents chemistry
Antirheumatic Agents pharmacokinetics
Bacterial Proteins metabolism
Disease Models, Animal
Dose-Response Relationship, Drug
Enzyme Inhibitors chemistry
Enzyme Inhibitors pharmacokinetics
Mice
Microbial Sensitivity Tests
Molecular Structure
Mycobacterium tuberculosis drug effects
Oxidoreductases metabolism
Papio
Phenyl Ethers chemistry
Phenyl Ethers pharmacokinetics
Structure-Activity Relationship
Time Factors
Tissue Distribution
Tuberculosis drug therapy
Tuberculosis microbiology
Anti-Bacterial Agents pharmacology
Antirheumatic Agents pharmacology
Bacterial Proteins antagonists & inhibitors
Enzyme Inhibitors pharmacology
Mycobacterium tuberculosis enzymology
Oxidoreductases antagonists & inhibitors
Phenyl Ethers pharmacology
Positron-Emission Tomography

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