title: Radiolabelling and positron emission tomography of PT70, a time-dependent inhibitor of InhA, the Mycobacterium tuberculosis enoyl-ACP reductase.
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.
authors.affiliation: Institute for Chemical Biology and Drug Discovery, Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, United States.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute for Chemical Biology and Drug Discovery, Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute for Chemical Biology and Drug Discovery, Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, United States.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Institute for Chemical Biology and Drug Discovery, Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, United States.
authors.forename: Pan
authors.initials: P
authors.lastname: Pan
authors.affiliation: Biological, Environmental and Climate Sciences Department, Brookhaven National Laboratory, Upton, NY 11973, United States.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
authors.affiliation: Biological, Environmental and Climate Sciences Department, Brookhaven National Laboratory, Upton, NY 11973, United States.
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Fowler
authors.affiliation: Institute for Chemical Biology and Drug Discovery, Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, United States. Electronic address: peter.tonge@stonybrook.edu.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Tonge
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010215:Papio; D010647:Phenyl Ethers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D013329:Structure-Activity Relationship; D013997:Time Factors; D014018:Tissue Distribution; D014376:Tuberculosis / Q000188:drug therapy / Q000382:microbiology
chemical_list: C549925:2-(2-tolyloxy)-5-hexylphenol; D000900:Anti-Bacterial Agents; D018501:Antirheumatic Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D010647:Phenyl Ethers; D010088:Oxidoreductases; C085257:InhA protein, Mycobacterium
keywords: Carbon-11; InhA enoyl-ACP reductase; PK–PD; Positron emission tomography; Residence time