SCIENTIFIC ACHIEVEMENT
X-ray diffraction data, collected at the Advanced Light Source (ALS) and other Department of Energy light sources, revealed the crystal structure of CMX410, a new compound that targets a key enzyme (Pks13) in the cell membrane of the bacterium responsible for tuberculosis (TB).
SIGNIFICANCE AND IMPACT
CMX410 is a promising new candidate to treat TB, including multidrug-resistant strains.
New treatments needed to tackle an old foe
TB is a deadly infectious disease caused by the bacterium Mycobacterium tuberculosis (Mtb). According to the World Health Organization, an estimated 10.8 million people contracted TB globally in 2023, and 1.25 million died from the disease. While antibiotics are effective for drug-sensitive TB cases, multidrug-resistant Mtb strains can evade common drug therapies.
Drug-resistant cases require a regimen that is often more expensive, toxic, and time-intensive. Patients are required to take six or more medications daily for up to 20 months. New approaches are urgently needed to shorten the course of drug interventions and address widespread multidrug-resistant strains.
A multi-institutional study led by researchers at Texas A&M University and the Calibr-Skaggs Institute for Innovative Medicine sought to find new treatments to address multidrug-resistant TB. The team screened a library of 406 compounds that belong to an active class of molecules [i.e., sulfur fluoride exchange (SuFEx)] to evaluate their efficacy against Mtb. The team developed one promising compound into CMX410, which targets Pks13, an enzyme essential for microbial cell wall biosynthesis.
Read more on the ALS website
Image: A cross-section of the crystal structure for the enzyme Pks13 (the surface colored pink and blue by hydrophobicity) as it interacts with CMX410 (shown as stick-like structure), a new drug candidate for TB
Credit: ALS
