TP0586532 explained

Drug Name:	TP0586532
Legal Status:	Investigational
C:	26
H:	28
N:	4
O:	4
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:	155294517
Chemspiderid:	115009295
Chembl:	4798122
Pdb Ligand:	H4R
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
Stdinchi:	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
Stdinchikey:	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

Notes and References

1. Ushiyama F, Takashima H, Matsuda Y, Ogata Y, Sasamoto N, Kurimoto-Tsuruta R, Ueki K, Tanaka-Yamamoto N, Endo M, Mima M, Fujita K, Takata I, Tsuji S, Yamashita H, Okumura H, Otake K, Sugiyama H . Lead optimization of 2-hydroxymethyl imidazoles as non-hydroxamate LpxC inhibitors: Discovery of TP0586532 . Bioorganic & Medicinal Chemistry . 30 . 115964 . January 2021 . 10.1016/j.bmc.2020.115964 . 33385955 .
2. Fujita K, Takata I, Yoshida I, Honma Y, Okumura H, Otake K, Takashima H, Sugiyama H . 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 . May 2022 . 10.1016/j.jiac.2022.01.004 . 35131156 .
3. Fujita K, Takata I, Yoshida I, Okumura H, Otake K, Takashima H, Sugiyama H . TP0586532, a non-hydroxamate LpxC inhibitor, has in vitro and in vivo antibacterial activities against Enterobacteriaceae . The Journal of Antibiotics . 75 . 2 . 98–107 . February 2022 . 10.1038/s41429-021-00486-3 . 34837061 .