History’s deadliest infectious disease has a new adversary. Although many think of tuberculosis as a disease of the past, it still kills 1.2 million people annually. Last month, scientists at Texas A&M AgriLife Research published a study in Nature, revealing that they had developed a new compound that could be a tuberculosis treatment breakthrough.
The new compound is called CMX410, and it targets the polyketide synthase 13 (Pks13) enzyme in Mycobacterium tuberculosis, which the bacteria use to build their cell wall. The compound was also found to be effective against drug-resistant tuberculosis infections.
Promising early results show minimal side effects
Pks13 has long been recognized as a potential target for tuberculosis treatments, but drug development efforts have failed to pass both safety and performance requirements. CMX410 is highly specific, which increases the safety of the treatment. The compound contains a reactive chemical group that forms an irreversible bond with a specific site on Pks13, thereby minimizing side effects. The addition of that group also reduces the likelihood of the bacteria becoming resistant to CMX410.
Scientists within Texas A&M AgriLife Research and Calibr-Skaggs have developed a new compound targeting a key bacterial enzyme on M. tuberculosis. The compound proved effective against even drug-resistant strains of tuberculosis in early studies. (Inna Krieger/Texas A&M AgriLife)
The researchers used a library of compounds shared by the Sharpless lab to identify molecules that could inhibit the growth of M. tuberculosis. Baiyuan Yang, Ph.D., associate director of medicinal chemistry, said the team examined more than 300 analogs for the optimal balance of potency, selectivity and safety.
CMX410 was tested against 66 strains of M. tuberculosis and found to be effective against both laboratory and multidrug-resistant strains collected from patients. The researchers also found that CMX410 could be safely combined with other tuberculosis antibiotics. That trait could be vital as treatment plans often require patients to take multiple drugs simultaneously for months at a time.
Researchers found no adverse effects in a 14-day rat toxicity study in doses up to 1,000 mg/kg per day. Additionally, because CMX410 is highly specific to its target, the researchers see disruptions to microbiomes and beneficial bacteria as unlikely.
Filed Under: Infectious Disease, Preclinical testing
