TP0586532

TP0586532

Legal status
Legal status	Investigational
Identifiers
IUPAC name 4-[(1R,5S)-6-[2-[4-[3-[[2-[(1S)-1-hydroxyethyl]imidazol-1-yl]methyl]-1,2-oxazol-5-yl]phenyl]ethynyl]-3-azabicyclo[3.1.0]hexan-3-yl]butanoic acid
CAS Number	2427584-96-9
PubChem CID	155294517
ChemSpider	115009295
ChEMBL	ChEMBL4798122
PDB ligand	H4R ( PDBe , RCSB PDB )
Chemical and physical data
Formula	C26H28N4O4
Molar mass	460.534 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[C@@H](C1=NC=CN1CC2=NOC(=C2)C3=CC=C(C=C3)C#CC4[C@H]5[C@@H]4CN(C5)CCCC(=O)O)O
InChI InChI=1S/C26H28N4O4/c1-17(31)26-27-10-12-30(26)14-20-13-24(34-28-20)19-7-4-18(5-8-19)6-9-21-22-15-29(16-23(21)22)11-2-3-25(32)33/h4-5,7-8,10,12-13,17,21-23,31H,2-3,11,14-16H2,1H3,(H,32,33)/t17-,21?,22-,23+/m0/s1 Key:PULUMLQUYYSBOR-BOSCWZPRSA-N

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]}

See also

• LPC-233

References

1. 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.
2. 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.
3. 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.