PBTZ169 is a new drug candicate that inhibits decaprenylphosphoryl-β-d-ribose 2′-oxidase (DprE1), more efficiently than BTZ043target: DprE1In vitro: PBTZ169, inhibit decaprenylphosphoryl-β-d-ribose 2′-oxidase (DprE1) and display nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro. [1]In vivo: PBTZ169 can be suspend in 0.25% hydroxy-propylmethyl-cellulose. The administertration for PBTZ169 is 100 mg/kg by gavage. The MIC50 and MIC90 values were 0.0075 and 0.030 ug/mL, respectively. The MIC for PBTZ169 for N. brasiliensis HUJEG-1 was 0.0037 ug/mL.[2] PBTZ169 has improved potency, safety and efficacy in zebrafish and mouse models of tuberculosis (TB). [3]
References:
[1]. [1] Makarov V et al. The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 from Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2015 Aug;59(8):4446-52.
[2]. [2] González-Martínez NA et al. In Vivo Activity of the Benzothiazinones PBTZ169 and BTZ043 against Nocardia brasiliensis. PLoS Negl Trop Dis. 2015 Oct 16;9(10):e0004022.
[3]. [3] Makarov V et al. Towards a new combination therapy for tuberculosis with next generation benzothiazinones.EMBO Mol Med. 2014 Mar;6(3):372-83.