DS86760016

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

DS86760016 是一种新型选择性细菌亮氨酰-tRNA 合成酶 (LeuRS) 抑制剂，IC50 为 0.38 uM（大肠杆菌，LeuRS）。

DS86760016 is a novel selective bacterial leucyl-tRNA synthetase (LeuRS) inhibitor with IC50 of 0.38 uM (Escherichia coli, LeuRS); inhibits Pseudomonas aeruginosa and Acinetobacter baumannii with IC50 of 0.62 and 0.16 uM, respectively; shows active against MDR Gram-negative bacteria (MIC 0.25-2 ug/mL) with an improved pharmacokinetic profile compared with GSK2251052; also shows lower mutant prevention concentrations against P. aeruginosa compared to GSK2251052.

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 MIC90 of 2 μg/ml.

DS86760016 (7.5-220 mg/kg; s.c.; q6h for 7 days) shows moderate spontaneous resistance (FSR).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 (CLp) of 11, 29, 5.6, and 4.5 ml/min/kg in mouse, rat, monkey, and dog plasma, respectively. The plasma half-lives (t1/2) 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 (DNAUCIVs) of 1.5, 0.6, 3.7, and 3.0 μg h kg/ml/mg in mice, rats, monkeys, and dogs, respectively. Animal Model:Immunocompetent female Swiss Webster mice (urinary tract infection, UTI model) 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.

DS 86760016

GPCR/G Protein

Antibacterial

Antibacterial

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1853176-89-2

243.45

C9H11BClNO4

>98% (HPLC)

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(S)-3-(aminomethyl)-[1,3]dioxolo[4',5':5,6]benzo[1,2-c][1,2]oxaborol-1(3H)-ol hydrochloride

(-20℃)

With Ice Pack

≥ 2 years