TP0586532 is an experimental antibiotic drug, which acts as a potent and selective inhibitor of the bacterial enzyme UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC). This enzyme is important for the production of Lipid A, a key component of the cell membrane of Gram-negative bacteria. Previous inhibitors of LpxC have failed to progress into clinical trials in humans, mostly because of off-target cardiovascular toxicity, so TP0586532 was based on a different structural class which is hoped to reduce this risk. In animal studies it shows activity against carbapenem-resistant Klebsiella pneumoniae but has not yet progressed into human trials.[1][2][3]
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| Formula | C26H28N4O4 |
| Molar mass | 460.534 g·mol−1 |
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See also
editReferences
edit- ^ Ushiyama F, Takashima H, Matsuda Y, Ogata Y, Sasamoto N, Kurimoto-Tsuruta R, et al. (January 2021). "Lead optimization of 2-hydroxymethyl imidazoles as non-hydroxamate LpxC inhibitors: Discovery of TP0586532". Bioorganic & Medicinal Chemistry. 30: 115964. doi:10.1016/j.bmc.2020.115964. PMID 33385955.
- ^ Fujita K, Takata I, Yoshida I, Honma Y, Okumura H, Otake K, et al. (May 2022). "Pharmacodynamic target assessment and prediction of clinically effective dosing regimen of TP0586532, a novel non-hydroxamate LpxC inhibitor, using a murine lung infection model". Journal of Infection and Chemotherapy. 28 (5): 635–642. doi:10.1016/j.jiac.2022.01.004. PMID 35131156.
- ^ Fujita K, Takata I, Yoshida I, Okumura H, Otake K, Takashima H, et al. (February 2022). "TP0586532, a non-hydroxamate LpxC inhibitor, has in vitro and in vivo antibacterial activities against Enterobacteriaceae". The Journal of Antibiotics. 75 (2): 98–107. doi:10.1038/s41429-021-00486-3. PMID 34837061.