TCA1

TCA1 is a small molecule with activity against drug-susceptible and -resistant Mycobacterium tuberculosis (Mtb). TCA1 inhibits enzymes involved in cell wall and molybdenum cofactor biosynthesis, such as DprE1 and MoeW^[1]. In Vitro: TCA1 shows bactericidal activity against both replicating (WT and drug resistant) and nonreplicating Mycobacterium tuberculosis (Mtb). TCA1 inhibits biofilm formation by Mtb H37Rv^[1].
TCA1 shows selective inhibitory activity against bacterial growth-it is inactive against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, suggesting that the target for its bactericidal activity is specific to the genus Mycobacterium^[1]. In Vivo: TCA1 (40 mg/kg; oral gavage; 1 time/d for 5 d/week; for 4 weeks) is efficacious in acute and chronic Mtb infection mouse models^[1].
In a mouse model of Mtb infection, after i.v. administration, TCA1 exhibits a low clearance and steady-state volume of distribution, with an elimination half-life of 0.73 h. After oral administration of 20 and 50 mg/kg in solution formulation, TCA1 shows a high C_max (2122 and 5653 nM, respectively), moderate exposure with oral bioavailability ranging from 19% to 46%, and a half-life of 1.8 h^[1]. BALB/c mice infected with Mtb H37Rv^[1] 40 mg/kg Oral gavage; 1 time/d for 5 d/week; for 4 weeks Effectively inhibits Mtb in vivo.