DS86760016 is a potent leucyl-tRNA synthetase (LeuRS) inhibitor with activity against multidrug-resistant (MDR) Gram-negative bacteria, such as Escherichia coli , Klebsiella pneumoniae , and Pseudomonas aeruginosa . DS86760016 inhibits LeuRS enzymes from Escherichia coli , Pseudomonas aeruginosa , and Acinetobacter baumannii , with IC 50 s of 0.38, 0.62, and 0.16 μM, respectively.

DS86760016 inhibits some Gram-negative bacteria with an MICs ranging from 0.25 to 2 μg/ml. The MIC of DS86760016 against Gram-positive bacteria is >32 μg/ml. DS86760016 is active against both susceptible and these MDR P. aeruginosa , E. coli , and K. pneumoniae strains, with an MIC 90 of 2 μg/ml[1].

DS86760016 (7.5-220 mg/kg; s.c.; q6h for 7 days) shows moderate spontaneous resistance (FSR)[1]. The pharmacokinetic (PK) parameters of DS86760016 in mouse, rat, monkey, and dog plasma by the intravenous (i.v.) route are test. DS86760016 shows lower intravenous plasma clearances (CL p ) of 11, 29, 5.6, and 4.5 ml/min/kg in mouse, rat, monkey, and dog plasma, respectively. The plasma half-lives (t 1/2 ) for DS86760016 are 1.9, 1.5, 8.6, and 8.3 h in mice, rats, monkeys, and dogs, respectively. The lower plasma clearance resulted in higher plasma exposures for DS86760016, with dose-normalized areas under the curve after i.v. administration (DNAUC IV s) of 1.5, 0.6, 3.7, and 3.0 μg h kg/ml/mg in mice, rats, monkeys, and dogs, respectively[1]. Animal Model: Immunocompetent female Swiss Webster mice (urinary tract infection, UTI model)[1]Dosage: 7.5, 30, 220 mg/kg Administration: S.c.; q6h for 7 days Result: Bacteria resistant to DS86760016 were detected in a few animals after 1 day of treatment at doses of 7.5 and 30 mg/kg q6h; however, no resistant bacteria were detected at these doses after 7 days of treatment. No resistance was observed in any of the mice treated at a dose of 220 mg/kg q6h.

1853176-89-2

C9H11BClNO4

243.45

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years