| Structural highlights
4a2z is a 1 chain structure with sequence from Leishmania major. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , ,
| | Related: | 4a32, 4a33, 2wsa, 4a30, 4a31 |
| Activity: | Glycylpeptide N-tetradecanoyltransferase, with EC number 2.3.1.97 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Publication Abstract from PubMed
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 (IC(50) = 2 nM) and T. brucei (EC(50) = 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.
Discovery of a novel class of orally active trypanocidal N-myristoyltransferase inhibitors.,Brand S, Cleghorn LA, 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 MA, Read KD, Wyatt PG, Gilbert IH J Med Chem. 2012 Jan 12;55(1):140-52. Epub 2011 Dec 7. PMID:22148754[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Brand S, Cleghorn LA, 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 MA, Read KD, Wyatt PG, Gilbert IH. Discovery of a novel class of orally active trypanocidal N-myristoyltransferase inhibitors. J Med Chem. 2012 Jan 12;55(1):140-52. Epub 2011 Dec 7. PMID:22148754 doi:10.1021/jm201091t
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