MedKoo product information:

BTZ043

The new antitubercular drug candidate 2-[2-S-methyl-1,4-dioxa-8-azaspiro[4.5]dec-8-yl]-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one (BTZ043) targets the DprE1 (Rv3790) subunit of the enzyme decaprenylphosphoryl-beta-d-ribose 2'-epimerase. To monitor the potential development of benzothiazinone (BTZ) resistance, a total of 240 sensitive and multidrug-resistant Mycobacterium tuberculosis clinical isolates from four European hospitals were surveyed for the presence of mutations in the dprE1 gene and for BTZ susceptibility. All 240 strains were susceptible, thus establishing the baseline prior to the introduction of BTZ043 in clinical trials.

BTZ043 – proved particularly effective against the tubercle bacillus. The latter’s cell walls, with their particular wax-rich structure, confer high resistance to antiseptics, some antibiotics and macrophages.

The new compound inhibits the enzyme which produces the molecule linking the various layers of the bacterial cell wall. “Without this enzyme, the bacterium explodes”, the Professor notes. Identifying this target was in itself the major discovery in this research as it paves the way for further therapeutic prospects. The research also relied on many advanced technologies developed by the EPFL. BTZ043 is now exiting preclinical research, soon to be the subject of clinical testing in humans. A new therapy could emerge in under 10 years.

Current developer:  the EPFL School of Life Sciences,

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