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.
Keywords:
Carbon-11; InhA enoyl-ACP reductase; PK–PD; Positron emission tomography; Residence time.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacokinetics
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Anti-Bacterial Agents / pharmacology*
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Antirheumatic Agents / chemistry
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Antirheumatic Agents / pharmacokinetics
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Antirheumatic Agents / pharmacology*
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Bacterial Proteins / antagonists & inhibitors*
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Bacterial Proteins / metabolism
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacokinetics
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Enzyme Inhibitors / pharmacology*
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Mice
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Microbial Sensitivity Tests
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Molecular Structure
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Mycobacterium tuberculosis / drug effects
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Mycobacterium tuberculosis / enzymology*
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Oxidoreductases / antagonists & inhibitors*
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Oxidoreductases / metabolism
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Papio
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Phenyl Ethers / chemistry
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Phenyl Ethers / pharmacokinetics
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Phenyl Ethers / pharmacology*
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Positron-Emission Tomography*
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Structure-Activity Relationship
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Time Factors
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Tissue Distribution
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Tuberculosis / drug therapy
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Tuberculosis / microbiology
Substances
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2-(2-tolyloxy)-5-hexylphenol
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Anti-Bacterial Agents
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Antirheumatic Agents
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Bacterial Proteins
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Enzyme Inhibitors
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Phenyl Ethers
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Oxidoreductases
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InhA protein, Mycobacterium