TCA1

• CAT Number: I045495
• CAS Number: 864941-32-2
• Molecular Formula: C16H13N3O4S2
• Molecular Weight: 375.42
• Purity: ≥95%
• Synonyms: ethyl N-[2-(1,3-benzothiazole-2-carbonylamino)thiophene-3-carbonyl]carbamate
• InChI: InChI=1S/C16H13N3O4S2/c1-2-23-16(22)19-12(20)9-7-8-24-14(9)18-13(21)15-17-10-5-3-4-6-11(10)25-15/h3-8H,2H2,1H3,(H,18,21)(H,19,20,22)
• InChIKey: ISNBJLXHBBZKSL-UHFFFAOYSA-N
• SMILES: CCOC(=O)NC(=O)C1=C(SC=C1)NC(=O)C2=NC3=CC=CC=C3S2

TCA1 is a small molecule with activity against agent-susceptible and -resistant Mycobacterium tuberculosis (Mtb). TCA1 inhibits enzymes involved in cell wall and molybdenum cofactor biosynthesis, such as DprE1 and MoeW[1].
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].
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 Cmax (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.

Reference

[1]. Feng Wang, et al. Identification of a small molecule with activity against drug-resistant and persistent tuberculosis. Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):E2510-7.
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