This article is more than 5 years old. Information may no longer be current.
Novel method identifies FDA-approved antacid as candidate TB treatment
Click Here to Manage Email Alerts
Using an automated drug discovery platform, researchers have identified the common over-the-counter antacid lansoprazole as a candidate treatment against Mycobacterium tuberculosis.
Stewart T. Cole, PhD, FRS, of the Ecole Polytechnique Fédérale de Lausanne, Switzerland, and colleagues examined a selection of drugs previously approved by the FDA to determine whether they may be repurposed as potential tuberculosis treatments. Using an automated, high-throughput system able to quickly introduce these compounds to cultured lung cells infected with M. tuberculosis, the researchers determined that the proton-pump inhibitor lansoprazole (LPZ) was active against multidrug-resistant tuberculosis (MDR-TB).
“Proton-pump inhibitors are both safe and widely sold around the world,” Cole said in a press release. “Being highly active against drug-resistant strains of M. tuberculosis, this novel class of drugs provides us with an excellent opportunity to treat tuberculosis.”
Stewart T. Cole
Interactions between the infected cells and the candidate treatment observed by the researchers ex vivo revealed that LPZ is converted by host cytoplasm into LPZ sulfide. This new analogue targets the cytochrome bc1 complex of TB and MDR-TB while sparing the human gastric H+K+ -ATPase, making LPZ a highly selective compound for targeting the infection. Along with positive pharmacokinetic evidence in mice and other previously presented data concerning FDA-approved LPZ, the researchers wrote that LPZ is an attractive option in the TB drug pipeline, and that these methods can be used to determine whether other substances also can be repurposed.
“The prodrug LPZ represents an excellent example of a valuable hit compound in an existing library that was missed by conventional drug screens,” the researchers wrote. “Our strategy of host-mediated prodrug activation is generally applicable to other drug-resistant bacterial pathogens, thereby enabling inhibitors with novel targets to be found in compound libraries that have been interrogated previously in standard phenotypic screens.” – by Dave Muoio
Disclosure s : Rybniker and Cole report being named as inventors on a patent pertaining to this work. The remaining authors report no relevant financial disclosures.
Collapse
Click Here to Manage Email Alerts