Dataset Information

Discovery of a novel class of orally active trypanocidal N-myristoyltransferase inhibitors.

ABSTRACT: 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.

SUBMITTER: Brand S

PROVIDER: S-EPMC3256935 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Discovery of a novel class of orally active trypanocidal N-myristoyltransferase inhibitors.

Brand Stephen S Cleghorn Laura A T LA McElroy Stuart P SP Robinson David A DA Smith Victoria C VC Hallyburton Irene I Harrison Justin R JR Norcross Neil R NR Spinks Daniel D Bayliss Tracy T Norval Suzanne S Stojanovski Laste L Torrie Leah S LS Frearson Julie A JA Brenk Ruth R Fairlamb Alan H AH Ferguson Michael A J MA Read Kevin D KD Wyatt Paul G PG Gilbert Ian H IH

Journal of medicinal chemistry 20111207 1

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 ex ...[more]

PMID: 22148754

Dataset Information

Discovery of a novel class of orally active trypanocidal N-myristoyltransferase inhibitors.

Publications

Discovery of a novel class of orally active trypanocidal N-myristoyltransferase inhibitors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Similar Datasets

Design and Synthesis of Brain Penetrant Trypanocidal N-Myristoyltransferase Inhibitors.
| S-EPMC5734605 | biostudies-literature

Discovery of Orally Active Hydroxyethylamine Based SPPL2a Inhibitors.
| S-EPMC6580379 | biostudies-literature

3-Amido-3-aryl-piperidines: A Novel Class of Potent, Selective, and Orally Active GlyT1 Inhibitors.
| S-EPMC4027785 | biostudies-literature

Discovery of novel diarylamides as orally active diuretics targeting urea transporters.
| S-EPMC7838058 | biostudies-literature

Discovery of Pyridopyrimidinones as Potent and Orally Active Dual Inhibitors of PI3K/mTOR.
| S-EPMC5846042 | biostudies-literature

Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB.
| S-EPMC2435229 | biostudies-literature

Discovery of novel and ligand-efficient inhibitors of Plasmodium falciparum and Plasmodium vivax N-myristoyltransferase.
| S-EPMC3601602 | biostudies-literature

Discovery of TAK-272: A Novel, Potent, and Orally Active Renin Inhibitor.
| S-EPMC5066151 | biostudies-literature

Discovery of Benzotriazolo[4,3-d][1,4]diazepines as Orally Active Inhibitors of BET Bromodomains.
| S-EPMC4753545 | biostudies-literature

Discovery of Orally Active Isofuranones as Potent, Selective Inhibitors of Hematopoetic Progenitor Kinase 1.
| S-EPMC7957935 | biostudies-literature