product name BTZ043 Racemate
Description: BTZ043 racemate is a decaprenylphosphoryl-β-D-ribose 2-epimerase (DprE1) inhibitor acting as a new antimycobacterial agent that kill Mycobacterium tuberculosis. BTZ043 displayed similar activity against all clinical isolates of M. tuberculosis that were tested, including extensively drug-resistant and multidrug-resistant strains, indicating that it targets a previously unknown biological function. BTZ043 is bactericidal, reducing viability in vitro by more than 1000-fold in under 72 hours, which is comparable to the INH killing effect.
References: Science. 2009 May 8;324(5928):801-4; Antimicrob Agents Chemother. 2012 Nov;56(11):5790-3.
Formula
CAS No.
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO:
Water: <1 mg/mL
Ethanol:
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: By targeting decaprenylphosphoryl-β-D-ribose 2-epimerase, BTZ043 abolishes the formation of decaprenylphosphoryl arabinose, leading to cell lysis and death of Mycobacterium tuberculosis. BTZ043 displays similar activity against all clinical isolates of M. tuberculosis, including multidrug-resistant and extensively drug-resistant strains. BTZ043 displays significant activity against M. tuberculosis H37Rv and Mycobacterium smegmatis with MIC of 1 ng/mL (2.3 nM) and 4 ng/mL (9.2 nM), respectively, which is more potent than those of the existing tuberculosis (TB) drugs isoniazid (INH) and ethambutol (EMB) with MIC of 0.02-0.2 μg/mL and 1-5 μg/mL, respectively. BTZ043 is less effective in two different model systems (auxotrophy and starvation) involving metabolically inert M. tuberculosis, indicating that BTZ043 blocks a step in active metabolism similar to isoniazid (INH). BTZ043 treatment in M. smegmatis cells decreases the growth rate rapidly followed by a swelling of the poles and lysis of the cells after a few hours, which is similar but delayed in M. tuberculosis. BTZ043 (1/4 MIC 0.375 ng/mL) in combination with TMC207 (1/4 MIC 20 ng/mL) has a stronger cidal effect on M. tuberculosis but not BTZ-resistant M. tuberculosis mutant than TMC207 alone at a concentration of 80 ng/mL. Kinase Assay: Cell Assay: BTZ043 displayed similar activity against all clinical isolates of M. tuberculosis that were tested, including extensively drug-resistant and multidrug-resistant strains, indicating that it targets a previously unknown biological function. BTZ043 is bactericidal, reducing viability in vitro by more than 1000-fold in under 72 hours, which is comparable to the INH killing effect. |
|---|---|
| In Vivo | In a mouse model of chronic tuberculosis, administration of BTZ043 at 37.5 mg/kg or 300 mg/kg for 4 weeks reduces the bacterial burden in the lungs and spleens by 1 and 2 logs, respectively. |
| Animal model | BALB/c mice infected with a low bacillary load (~200 CFU) of M. tuberculosis H37Rv via aerosol |
| Formulation & Dosage | Formulated in carboxymethyl cellulose formulation (0.25%); 37.5 mg/kg, or 300 mg/kg; p.o. once a day |
| References | Science. 2009 May 8;324(5928):801-4; Antimicrob Agents Chemother. 2012 Nov;56(11):5790-3. |
