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

Hui Wang; Li Liu; Yang Lu; Pan Pan; Jacob M. Hooker; Joanna S. Fowler; Peter J. Tonge

doi:10.1016/j.bmcl.2015.07.019

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

Hui Wang
, Li Liu
, Yang Lu
, Pan Pan
, Jacob M. Hooker
, Joanna S. Fowler
, Peter J. Tonge

Chemistry

Stony Brook University

Stony Brook University
Center for Biotechnology
Frontage Laboratories
Arkema group
Brookhaven National Laboratory
Massachusetts General Hospital

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English
Pages (from-to)	4782-4786
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	25
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2015.07.019
State	Published - Nov 1 2015

Keywords

Carbon-11
InhA enoyl-ACP reductase
PK-PD
Positron emission tomography
Residence time

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10.1016/j.bmcl.2015.07.019

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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.",

keywords = "Carbon-11, InhA enoyl-ACP reductase, PK-PD, Positron emission tomography, Residence time",

author = "Hui Wang and Li Liu and Yang Lu and Pan Pan and Hooker, \{Jacob M.\} and Fowler, \{Joanna S.\} and Tonge, \{Peter J.\}",

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doi = "10.1016/j.bmcl.2015.07.019",

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T1 - Radiolabelling and positron emission tomography of PT70, a time-dependent inhibitor of InhA, the Mycobacterium tuberculosis enoyl-ACP reductase

AU - Wang, Hui

AU - Liu, Li

AU - Lu, Yang

AU - Pan, Pan

AU - Hooker, Jacob M.

AU - Fowler, Joanna S.

AU - Tonge, Peter J.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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.

AB - 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.

KW - Carbon-11

KW - InhA enoyl-ACP reductase

KW - PK-PD

KW - Positron emission tomography

KW - Residence time

UR - https://www.scopus.com/pages/publications/84944274834

U2 - 10.1016/j.bmcl.2015.07.019

DO - 10.1016/j.bmcl.2015.07.019

M3 - Article

C2 - 26227776

SN - 0960-894X

VL - 25

SP - 4782

EP - 4786

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 21

ER -

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

Abstract

Keywords

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