AN3365 (hydrochloride) (Synonyms: Epetraborole,GSK2251052)

AN3365 is a potent and selective leucyl-tRNA synthetase inhibitor [1].

The leucyl-tRNA synthetase belongs to a member of the class I aminoacyl-tRNA synthetase family. The leucyl-tRNA synthetase has been involved in catalyzing the ATP-dependent ligation of L-leucine to tRNA. It has been found in the cytoplasm as part of a multisynthetase complex and interacts with the arginine tRNA synthetase through its C-terminal domain [2].

AN3365 potently and selectively inhibited bacterial leucyl-tRNA synthetase activity against Gram-negative bacteria. AN3365 was a member of a novel class of boron-containing compounds, the aminomethyl benzoxoaboroles, which showed potential to combat multidrug resistance. AN3365 was active against many microbial strains, including strains of Enterobacteriaceae with the MIC50/90 of 0.5/1 μg/ml. AN3365 showed activity against the non-fermentative Gram-negative clinical isolates P. aeruginosa, A. baumannii, S. maltophilia, and B. cepacid with the MIC50/90s of 4/8, 4/8, 2/4, and 8/32 μg/ml, respectively [1].

References:
[1] Hernandez V, Crépin T, Palencia A, et al.  Discovery of a novel class of boron-based antibacterials with activity against gram-negative bacteria[J]. Antimicrobial agents and chemotherapy, 2013, 57(3): 1394-1403.
[2] Rouget P, Chapeville F.  Leucyl‐tRNA Synthetase[J]. European journal of biochemistry, 1971, 23(3): 443-451.