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:
-
- Stony Brook Univ., NY (United States)
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Publication Date:
- Research Org.:
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Sponsoring Org.:
- National Institute of Health
- OSTI Identifier:
- 1239783
- Report Number(s):
- BNL-111671-2015-JA
Journal ID: ISSN 0960-894X; R&D Project: MO-085; KP1503010
- Grant/Contract Number:
- SC00112704
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Bioorganic and Medicinal Chemistry Letters
- Additional Journal Information:
- Journal Volume: 25; Journal Issue: 21; Journal ID: ISSN 0960-894X
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; Positron emission tomography; InhA enoyl-ACP reductase; Residence time; Carbon-11; PK-PD
Citation Formats
Wang, Hui, Liu, Li, Lu, Yang, Pan, Pan, Hooker, Jacob M., Fowler, Joanna S., and Tonge, Peter J. Radiolabelling and positron emission tomography of PT70, a time-dependent inhibitor of InhA, the Mycobacterium tuberculosis enoyl-ACP reductase. United States: N. p., 2015.
Web. doi:10.1016/j.bmcl.2015.07.019.
Wang, Hui, Liu, Li, Lu, Yang, Pan, Pan, Hooker, Jacob M., Fowler, Joanna S., & Tonge, Peter J. Radiolabelling and positron emission tomography of PT70, a time-dependent inhibitor of InhA, the Mycobacterium tuberculosis enoyl-ACP reductase. United States. https://doi.org/10.1016/j.bmcl.2015.07.019
Wang, Hui, Liu, Li, Lu, Yang, Pan, Pan, Hooker, Jacob M., Fowler, Joanna S., and Tonge, Peter J. Tue .
"Radiolabelling and positron emission tomography of PT70, a time-dependent inhibitor of InhA, the Mycobacterium tuberculosis enoyl-ACP reductase". United States. https://doi.org/10.1016/j.bmcl.2015.07.019. https://www.osti.gov/servlets/purl/1239783.
@article{osti_1239783,
title = {Radiolabelling and positron emission tomography of PT70, a time-dependent inhibitor of InhA, the Mycobacterium tuberculosis enoyl-ACP reductase},
author = {Wang, Hui and Liu, Li and Lu, Yang and Pan, Pan and Hooker, Jacob M. and Fowler, Joanna S. and Tonge, Peter J.},
abstractNote = {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.},
doi = {10.1016/j.bmcl.2015.07.019},
journal = {Bioorganic and Medicinal Chemistry Letters},
number = 21,
volume = 25,
place = {United States},
year = {Tue Jul 14 00:00:00 EDT 2015},
month = {Tue Jul 14 00:00:00 EDT 2015}
}
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Works referenced in this record:
Radiosynthesis and Bioimaging of the Tuberculosis Chemotherapeutics Isoniazid, Rifampicin and Pyrazinamide in Baboons
journal, April 2010
- Liu, Li; Xu, Youwen; Shea, Colleen
- Journal of Medicinal Chemistry, Vol. 53, Issue 7
The Fight Against Tuberculosis
journal, June 2006
- Scheindlin, S.
- Molecular Interventions, Vol. 6, Issue 3
The WHO 2014 Global tuberculosis report—further to go
journal, January 2015
- Zumla, Alimuddin; George, Andrew; Sharma, Virendra
- The Lancet Global Health, Vol. 3, Issue 1
Global tuberculosis control: lessons learnt and future prospects
journal, May 2012
- Lienhardt, Christian; Glaziou, Philippe; Uplekar, Mukund
- Nature Reviews Microbiology, Vol. 10, Issue 6
Extensively drug-resistant tuberculosis: current challenges and threats
journal, July 2008
- Jain, Amita; Mondal, Rajesh
- FEMS Immunology & Medical Microbiology, Vol. 53, Issue 2
inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis
journal, January 1994
- Banerjee, A.; Dubnau, E.; Quemard, A.
- Science, Vol. 263, Issue 5144
The isoniazid-NAD adduct is a slow, tight-binding inhibitor of InhA, the Mycobacterium tuberculosis enoyl reductase: Adduct affinity and drug resistance
journal, November 2003
- Rawat, R.; Whitty, A.; Tonge, P. J.
- Proceedings of the National Academy of Sciences, Vol. 100, Issue 24
The catalase—peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis
journal, August 1992
- Zhang, Ying; Heym, Beate; Allen, Bryan
- Nature, Vol. 358, Issue 6387
Studies on the Mechanism of Action of Isoniazid and Ethionamide in the Chemotherapy of Tuberculosis
journal, May 1995
- Johnsson, Kai; King, David S.; Schultz, Peter G.
- Journal of the American Chemical Society, Vol. 117, Issue 17
Kinetics of Inactivation of WT and C243S Mutant of Mycobacterium tuberculosis Enoyl Reductase by Activated Isoniazid
journal, January 1996
- Basso, Luiz A.; Zheng, Renjian; Blanchard, John S.
- Journal of the American Chemical Society, Vol. 118, Issue 45
Implications of multidrug resistance for the future of short-course chemotherapy of tuberculosis: a molecular study
journal, July 1994
- Heym, B.; Honoré, N.; Schurra, C.
- The Lancet, Vol. 344, Issue 8918
Catalase-Peroxidase Gene Sequences in Isoniazid-Sensitive and -Resistant Strains of Mycobacterium tuberculosis from New York City
journal, October 1993
- Stoeckle, M. Y.; Guan, L.; Riegler, N.
- Journal of Infectious Diseases, Vol. 168, Issue 4
Characterization of the Catalase-Peroxidase Gene (katG) and inhA Locus in Isoniazid-Resistant and -Susceptible Strains of Mycobacterium tuberculosis by Automated DNA Sequencing: Restricted Array of Mutations Associated with Drug Resistance
journal, January 1996
- Musser, James M.; Kapur, Vivek; Williams, Diana L.
- The Journal of Infectious Diseases, Vol. 173, Issue 1
Mycobacterium tuberculosis Growth at theCavity Surface: a Microenvironment with FailedImmunity
journal, December 2003
- Kaplan, Gilla; Post, Frank A.; Moreira, Andre L.
- Infection and Immunity, Vol. 71, Issue 12
Design, Synthesis, and Evaluation of New Thiadiazole-Based Direct Inhibitors of Enoyl Acyl Carrier Protein Reductase (InhA) for the Treatment of Tuberculosis
journal, December 2014
- Šink, Roman; Sosič, Izidor; Živec, Matej
- Journal of Medicinal Chemistry, Vol. 58, Issue 2
A Virtual Screen Discovers Novel, Fragment-Sized Inhibitors of Mycobacterium tuberculosis InhA
journal, February 2015
- Perryman, Alexander L.; Yu, Weixuan; Wang, Xin
- Journal of Chemical Information and Modeling, Vol. 55, Issue 3
Direct inhibitors of InhA are active against Mycobacterium tuberculosis
journal, January 2015
- Manjunatha, U. H.; S. Rao, S. P.; Kondreddi, R. R.
- Science Translational Medicine, Vol. 7, Issue 269
Novel Inhibitors of InhA Efficiently Kill Mycobacterium tuberculosis under Aerobic and Anaerobic Conditions
journal, May 2011
- Vilchèze, Catherine; Baughn, Anthony D.; Tufariello, JoAnn
- Antimicrobial Agents and Chemotherapy, Vol. 55, Issue 8
Triclosan Derivatives: Towards Potent Inhibitors of Drug-Sensitive and Drug-Resistant Mycobacterium tuberculosis
journal, February 2009
- Freundlich, Joel S.; Wang, Feng; Vilchèze, Catherine
- ChemMedChem, Vol. 4, Issue 2
High Affinity InhA Inhibitors with Activity against Drug-Resistant Strains of Mycobacterium tuberculosis
journal, February 2006
- Sullivan, Todd J.; Truglio, James J.; Boyne, Melissa E.
- ACS Chemical Biology, Vol. 1, Issue 1
Slow-Onset Inhibition of the FabI Enoyl Reductase from Francisella tularensis : Residence Time and in Vivo Activity
journal, February 2009
- Lu, Hao; England, Kathleen; am Ende, Christopher
- ACS Chemical Biology, Vol. 4, Issue 3
Drug–target residence time and its implications for lead optimization
journal, August 2006
- Copeland, Robert A.; Pompliano, David L.; Meek, Thomas D.
- Nature Reviews Drug Discovery, Vol. 5, Issue 9
Drug–target residence time: critical information for lead optimization
journal, August 2010
- Lu, Hao; Tonge, Peter J.
- Current Opinion in Chemical Biology, Vol. 14, Issue 4
Translating slow-binding inhibition kinetics into cellular and in vivo effects
journal, April 2015
- Walkup, Grant K.; You, Zhiping; Ross, Philip L.
- Nature Chemical Biology, Vol. 11, Issue 6
Structural basis and mechanism of enoyl reductase inhibition by triclosan
journal, April 1999
- Stewart, Michael J.; Parikh, Sapan; Xiao, Guoping
- Journal of Molecular Biology, Vol. 290, Issue 4
A Slow, Tight Binding Inhibitor of InhA, the Enoyl-Acyl Carrier Protein Reductase from Mycobacterium tuberculosis
journal, March 2010
- Luckner, Sylvia R.; Liu, Nina; am Ende, Christopher W.
- Journal of Biological Chemistry, Vol. 285, Issue 19
Kinetic and Structural Characteristics of the Inhibition of Enoyl (Acyl Carrier Protein) Reductase by Triclosan ‡
journal, September 1999
- Ward, Walter H. J.; Holdgate, Geoffrey A.; Rowsell, Siân
- Biochemistry, Vol. 38, Issue 38
A Structural and Energetic Model for the Slow-Onset Inhibition of the Mycobacterium tuberculosis Enoyl-ACP Reductase InhA
journal, March 2014
- Li, Huei-Jiun; Lai, Cheng-Tsung; Pan, Pan
- ACS Chemical Biology, Vol. 9, Issue 4
Time-Dependent Diaryl Ether Inhibitors of InhA: Structure-Activity Relationship Studies of Enzyme Inhibition, Antibacterial Activity, and in vivo Efficacy
journal, March 2014
- Pan, Pan; Knudson, Susan E.; Bommineni, Gopal R.
- ChemMedChem, Vol. 9, Issue 4
Methods to Assess Tissue-Specific Distribution and Metabolism of Drugs
journal, December 2004
- Langer, Oliver; Muller, Markus
- Current Drug Metabolism, Vol. 5, Issue 6
Issues in Pharmacokinetics and Pharmacodynamics of Anti-Infective Agents: Distribution in Tissue
journal, May 2004
- Müller, Markus; dela Peña, Amparo; Derendorf, Hartmut
- Antimicrobial Agents and Chemotherapy, Vol. 48, Issue 5
Meta-Analysis of Clinical Studies Supports the Pharmacokinetic Variability Hypothesis for Acquired Drug Resistance and Failure of Antituberculosis Therapy
journal, March 2012
- Pasipanodya, Jotam G.; Srivastava, Shashikant; Gumbo, Tawanda
- Clinical Infectious Diseases, Vol. 55, Issue 2
The Role of Positron Emission Tomography in Pharmacokinetic Analysis
journal, January 1997
- Fischman, Alan J.; Alpert, Nathaniel M.; Babich, John W.
- Drug Metabolism Reviews, Vol. 29, Issue 4
Determining target engagement in living systems
journal, March 2013
- Simon, Gabriel M.; Niphakis, Micah J.; Cravatt, Benjamin F.
- Nature Chemical Biology, Vol. 9, Issue 4
Imaging Enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography
journal, October 2014
- Weinstein, E. A.; Ordonez, A. A.; DeMarco, V. P.
- Science Translational Medicine, Vol. 6, Issue 259
Radiosynthesis and biological evaluation of a novel enoyl-ACP reductase inhibitor for Staphylococcus aureus
journal, December 2014
- Wang, Hui; Lu, Yang; Liu, Li
- European Journal of Medicinal Chemistry, Vol. 88
Noninvasive Determination of 2-[ 18 F]-Fluoroisonicotinic Acid Hydrazide Pharmacokinetics by Positron Emission Tomography in Mycobacterium tuberculosis-Infected Mice
journal, September 2012
- Weinstein, E. A.; Liu, L.; Ordonez, A. A.
- Antimicrobial Agents and Chemotherapy, Vol. 56, Issue 12
Synthesis of 11 C, 18 F, 15 O, and 13 N Radiolabels for Positron Emission Tomography
journal, November 2008
- Miller, Philip W.; Long, Nicholas J.; Vilar, Ramon
- Angewandte Chemie International Edition, Vol. 47, Issue 47
Substituted diphenyl ethers as a broad-spectrum platform for the development of chemotherapeutics for the treatment of tularaemia
journal, September 2009
- England, K.; am Ende, C.; Lu, H.
- Journal of Antimicrobial Chemotherapy, Vol. 64, Issue 5
Works referencing / citing this record:
Improved synthesis of SV2A targeting radiotracer [11C]UCB-J
journal, November 2019
- Rokka, Johanna; Schlein, Eva; Eriksson, Jonas
- EJNMMI Radiopharmacy and Chemistry, Vol. 4, Issue 1