macozinone

Macozinone is a small molecule anti-tuberculosis drug candidate belonging to the piperazine-benzothiazinone class. It was optimized from the lead compound BTZ043 and is also known as PBTZ169. Macozinone specifically targets the essential flavoenzyme DprE1 in Mycobacterium tuberculosis by forming a covalent bond with the active-site cysteine (Cys387) of DprE1. This action blocks synthesis of decaprenyl phosphoarabinose (DPA), an essential precursor for cell wall arabinan biosynthesis in mycobacteria. The resulting inhibition leads to cell wall disruption and lysis of M. tuberculosis[4][5][7]. Macozinone has shown potent activity against both drug-sensitive and multidrug-resistant strains of tuberculosis and demonstrates additive or synergistic effects with other TB drugs such as bedaquiline and clofazimine[2]. Clinical development has included Phase 1/2 studies in healthy volunteers and patients with drug-sensitive TB[5][6].

Brand names

Macozinone

Other names

2-[4-(cyclohexylmethyl)piperazin-1-yl]-8-nitro-6-(trifluoromethyl)-4H-benzo[e][1,3]thiazin-4-one