LPC-233

LPC-233
Identifiers
	IUPAC name 4-(4-cyclopropylbuta-1,3-diynyl)-N-[(2S,3S)-4,4-difluoro-3-hydroxy-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]benzamide;
CAS Number	2142075-09-8;
PubChem CID	132060142;
PDB ligand	UFX (PDBe, RCSB PDB);
Chemical and physical data
Formula	C19H18F2N2O4
Molar mass	376.360 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@]([C@@H](C(=O)NO)NC(=O)C1=CC=C(C=C1)C#CC#CC2CC2)(C(F)F)O;
	InChI InChI=1S/C19H18F2N2O4/c1-19(26,18(20)21)15(17(25)23-27)22-16(24)14-10-8-13(9-11-14)5-3-2-4-12-6-7-12/h8-12,15,18,26-27H,6-7H2,1H3,(H,22,24)(H,23,25)/t15-,19+/m1/s1; Key:NPTNDHDCCLLFJE-BEFAXECRSA-N;

LPC-233 is an experimental antibiotic drug. It acts as a potent and selective inhibitor of the bacterial enzyme UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC), which is important for the production of Lipid A, a key component of the cell membrane of Gram-negative bacteria. Various inhibitors of LpxC have been developed but none have yet progressed into clinical trials in humans, mostly because of off-target cardiovascular toxicity.^[1]^[2]^[3] LPC-233 is one of the most advanced drugs of this type in preclinical testing, showing activity against several pathogens of concern such as multidrug-resistant Pseudomonas aeruginosa and carbapenem resistant Enterobacter strains, and with no cardiovascular toxicity evident in testing on mice and dogs.^[4]^[5]

References

^ Kalinin DV, Holl R (2016). "Insights into the Zinc-Dependent Deacetylase LpxC: Biochemical Properties and Inhibitor Design". Current Topics in Medicinal Chemistry. 16 (21): 2379–2430. doi:10.2174/1568026616666160413135835. PMID 27072691.
^ Kalinin DV, Holl R (November 2017). "LpxC inhibitors: a patent review (2010-2016)". Expert Opinion on Therapeutic Patents. 27 (11): 1227–1250. doi:10.1080/13543776.2017.1360282. PMID 28742403.
^ Niu Z, Lei P, Wang Y, Wang J, Yang J, Zhang J (May 2023). "Small molecule LpxC inhibitors against gram-negative bacteria: Advances and future perspectives". European Journal of Medicinal Chemistry. 253: 115326. doi:10.1016/j.ejmech.2023.115326. PMID 37023679.
^ Zhao J, Cochrane CS, Najeeb J, Gooden D, Sciandra C, Fan P, et al. (August 2023). "Preclinical safety and efficacy characterization of an LpxC inhibitor against Gram-negative pathogens". Science Translational Medicine. 15 (708): eadf5668. doi:10.1126/scitranslmed.adf5668. PMC 10785772. PMID 37556556.
^ Crunkhorn S (October 2023). "LpxC inhibitor eliminates bacterial infections". Nature Reviews. Drug Discovery. 22 (10): 787. doi:10.1038/d41573-023-00144-3. PMID 37666971.

[1] Kalinin DV, Holl R (2016). "Insights into the Zinc-Dependent Deacetylase LpxC: Biochemical Properties and Inhibitor Design". Current Topics in Medicinal Chemistry. 16 (21): 2379–2430. doi:10.2174/1568026616666160413135835. PMID 27072691.

[2] Kalinin DV, Holl R (November 2017). "LpxC inhibitors: a patent review (2010-2016)". Expert Opinion on Therapeutic Patents. 27 (11): 1227–1250. doi:10.1080/13543776.2017.1360282. PMID 28742403.

[3] Niu Z, Lei P, Wang Y, Wang J, Yang J, Zhang J (May 2023). "Small molecule LpxC inhibitors against gram-negative bacteria: Advances and future perspectives". European Journal of Medicinal Chemistry. 253: 115326. doi:10.1016/j.ejmech.2023.115326. PMID 37023679.

[4] Zhao J, Cochrane CS, Najeeb J, Gooden D, Sciandra C, Fan P, et al. (August 2023). "Preclinical safety and efficacy characterization of an LpxC inhibitor against Gram-negative pathogens". Science Translational Medicine. 15 (708): eadf5668. doi:10.1126/scitranslmed.adf5668. PMC 10785772. PMID 37556556.

[5] Crunkhorn S (October 2023). "LpxC inhibitor eliminates bacterial infections". Nature Reviews. Drug Discovery. 22 (10): 787. doi:10.1038/d41573-023-00144-3. PMID 37666971.

[1]

[2]

[3]

[4]

[5]

Identifiers

IUPAC name 4-(4-cyclopropylbuta-1,3-diynyl)-N-[(2S,3S)-4,4-difluoro-3-hydroxy-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]benzamide
CAS Number	2142075-09-8
PubChem CID	132060142
PDB ligand	UFX (PDBe, RCSB PDB)
Chemical and physical data
Formula	C₁₉H₁₈F₂N₂O₄
Molar mass	376.360 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES C[C@]([C@@H](C(=O)NO)NC(=O)C1=CC=C(C=C1)C#CC#CC2CC2)(C(F)F)O
InChI InChI=1S/C19H18F2N2O4/c1-19(26,18(20)21)15(17(25)23-27)22-16(24)14-10-8-13(9-11-14)5-3-2-4-12-6-7-12/h8-12,15,18,26-27H,6-7H2,1H3,(H,22,24)(H,23,25)/t15-,19+/m1/s1 Key:NPTNDHDCCLLFJE-BEFAXECRSA-N

LPC-233

See also

References