Discovery - University of Dundee - Online Publications

Library & Learning Centre

Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors

Standard

Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors. / Brand, Stephen; Cleghorn, Laura A. T.; McElroy, Stuart P.; Robinson, David A.; Smith, Victoria C.; Hallyburton, Irene; Harrison, Justin R.; Norcross, Neil R.; Spinks, Daniel; Bayliss, Tracy; Norval, Suzanne; Stojanovski, Laste; Torrie, Leah S.; Frearson, Julie A.; Brenk, Ruth; Fairlamb, Alan H.; Ferguson, Michael A. J.; Read, Kevin D.; Wyatt, Paul G.; Gilbert, Ian H. (Lead / Corresponding author).

In: Journal of Medicinal Chemistry, Vol. 55, No. 1, 12.01.2012, p. 140-152.

Research output: Contribution to journalArticle

Harvard

Brand, S, Cleghorn, LAT, McElroy, SP, Robinson, DA, Smith, VC, Hallyburton, I, Harrison, JR, Norcross, NR, Spinks, D, Bayliss, T, Norval, S, Stojanovski, L, Torrie, LS, Frearson, JA, Brenk, R, Fairlamb, AH, Ferguson, MAJ, Read, KD, Wyatt, PG & Gilbert, IH 2012, 'Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors' Journal of Medicinal Chemistry, vol 55, no. 1, pp. 140-152., 10.1021/jm201091t

APA

Brand, S., Cleghorn, L. A. T., McElroy, S. P., Robinson, D. A., Smith, V. C., Hallyburton, I., ... Gilbert, I. H. (2012). Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors. Journal of Medicinal Chemistry, 55(1), 140-152. 10.1021/jm201091t

Vancouver

Brand S, Cleghorn LAT, McElroy SP, Robinson DA, Smith VC, Hallyburton I et al. Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors. Journal of Medicinal Chemistry. 2012 Jan 12;55(1):140-152. Available from: 10.1021/jm201091t

Author

Brand, Stephen; Cleghorn, Laura A. T.; McElroy, Stuart P.; Robinson, David A.; Smith, Victoria C.; Hallyburton, Irene; Harrison, Justin R.; Norcross, Neil R.; Spinks, Daniel; Bayliss, Tracy; Norval, Suzanne; Stojanovski, Laste; Torrie, Leah S.; Frearson, Julie A.; Brenk, Ruth; Fairlamb, Alan H.; Ferguson, Michael A. J.; Read, Kevin D.; Wyatt, Paul G.; Gilbert, Ian H. (Lead / Corresponding author) / Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors.

In: Journal of Medicinal Chemistry, Vol. 55, No. 1, 12.01.2012, p. 140-152.

Research output: Contribution to journalArticle

Bibtex - Download

@article{0901640bb51e4183be5c0beb292aab5c,
title = "Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors",
keywords = "CANDIDA-ALBICANS, TRYPANOSOMA-BRUCEI, DRUG DISCOVERY, PEPTIDOMIMETIC INHIBITORS, SELECTIVE INHIBITORS, DIPEPTIDE AMIDES, PROTEIN, DESIGN, POTENT, BENZOFURANS",
author = "Stephen Brand and Cleghorn, {Laura A. T.} and McElroy, {Stuart P.} and Robinson, {David A.} and Smith, {Victoria C.} and Irene Hallyburton and Harrison, {Justin R.} and Norcross, {Neil R.} and Daniel Spinks and Tracy Bayliss and Suzanne Norval and Laste Stojanovski and Torrie, {Leah S.} and Frearson, {Julie A.} and Ruth Brenk and Fairlamb, {Alan H.} and Ferguson, {Michael A. J.} and Read, {Kevin D.} and Wyatt, {Paul G.} and Gilbert, {Ian H.}",
year = "2012",
month = "1",
doi = "10.1021/jm201091t",
volume = "55",
pages = "140--152",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "1",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors

AU - Brand,Stephen

AU - Cleghorn,Laura A. T.

AU - McElroy,Stuart P.

AU - Robinson,David A.

AU - Smith,Victoria C.

AU - Hallyburton,Irene

AU - Harrison,Justin R.

AU - Norcross,Neil R.

AU - Spinks,Daniel

AU - Bayliss,Tracy

AU - Norval,Suzanne

AU - Stojanovski,Laste

AU - Torrie,Leah S.

AU - Frearson,Julie A.

AU - Brenk,Ruth

AU - Fairlamb,Alan H.

AU - Ferguson,Michael A. J.

AU - Read,Kevin D.

AU - Wyatt,Paul G.

AU - Gilbert,Ian H.

PY - 2012/1/12

Y1 - 2012/1/12

N2 - <p>N-Myristoyltransferase (NMT) represents a promising drug target for human African trypanosomiasis (HAT), which is caused by the parasitic protozoa Trypanosoma brucei. We report the optimization of a high throughput screening hit (1) to give a lead molecule DDD85646 (63), which has potent activity against the enzyme (IC50 = 2 nM) and T. brucei (EC50 = 2 nM) in culture. The compound has good oral pharmacokinetics and cures rodent models of peripheral HAT infection. This compound provides an excellent tool for validation of T. brucei NMT as a drug target for HAT as well as a valuable lead for further optimization.</p>

AB - <p>N-Myristoyltransferase (NMT) represents a promising drug target for human African trypanosomiasis (HAT), which is caused by the parasitic protozoa Trypanosoma brucei. We report the optimization of a high throughput screening hit (1) to give a lead molecule DDD85646 (63), which has potent activity against the enzyme (IC50 = 2 nM) and T. brucei (EC50 = 2 nM) in culture. The compound has good oral pharmacokinetics and cures rodent models of peripheral HAT infection. This compound provides an excellent tool for validation of T. brucei NMT as a drug target for HAT as well as a valuable lead for further optimization.</p>

KW - CANDIDA-ALBICANS

KW - TRYPANOSOMA-BRUCEI

KW - DRUG DISCOVERY

KW - PEPTIDOMIMETIC INHIBITORS

KW - SELECTIVE INHIBITORS

KW - DIPEPTIDE AMIDES

KW - PROTEIN

KW - DESIGN

KW - POTENT

KW - BENZOFURANS

UR - http://www.scopus.com/inward/record.url?scp=84855848964&partnerID=8YFLogxK

U2 - 10.1021/jm201091t

DO - 10.1021/jm201091t

M3 - Article

VL - 55

SP - 140

EP - 152

JO - Journal of Medicinal Chemistry

T2 - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 1

ER -

Documents

Open Access permissions

Open

Documents

  • Publisher's final version

    Final published version, 4 MB, PDF-document

    Reprinted with permission from Brand, S, Cleghorn, LAT, McElroy, SP, Robinson, DA, Smith, VC, Hallyburton, I, Harrison, JR, Norcross, NR, Spinks, D, Bayliss, T, Norval, S, Stojanovski, L, Torrie, LS, Frearson, JA, Brenk, R, Fairlamb, AH, Ferguson, MAJ, Read, KD, Wyatt, PG & Gilbert, IH 2012, 'Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors' Journal of Medicinal Chemistry, vol 55, no. 1, pp. 140-152.. Copyright 2012 American Chemical Society.

Links

DOI

Library & Learning Centre

Contact | Accessibility | Policy