DprE1-IN-1 is a potent DprE1 inhibitor, with ic50 of 10 nM, also inhibits PDE6, with IC50 of 6 uM.IC50 value: 10 nM [1]Target: DprE1in vitro: DprE1-IN-1 demonstrats efficacy in a rodent model of tuberculosis, making it promising for further development.[1]in vivo: The pharmacokinetic profile of DprE1-IN-1 as a representative of the series in mice, rats, and dogs was determined after i.v. and oral dosing. DprE1-IN-1 shows oral bioavailabilities of 86% and 100% in rats and dogs, respectively. The oral exposures of DprE1-IN-1, assessed in infected animals, shows AUCs ranging from 166 to 240 uM . h, and free plasma concentrations were maintained above the MIC for 10 to 24 h. [2]
References:
[1]. Shirude PS, et al. Lead optimization of 1,4-azaindoles as antimycobacterial agents. J Med Chem. 2014 Jul 10;57(13):5728-37.
[2]. Chatterji M, et al. 1,4-azaindole, a potential drug candidate for treatment of tuberculosis. Antimicrob Agents Chemother. 2014 Sep;58(9):5325-31.