Product Detail

Development of novel therapeutic regimen for treating drug sensitive and resistant strains including MDR and XDR strains of tuberculosis involving Pranlukast PRK , a novel anti-tubercular agent in combination with rifampicin RIF and isoniazid INH

Title: • We discovered a novel allosteric site at the surface of ArgJ tetramer of Mtb. • Identified in –silico potential inhibitors for it from FDA approved drugs • Inhibitors were validated by inhibition of the purified enzyme • Pranlukast inhibited Mtb growth in cultures, in macrophage infection model and in mice in vivo. • PRK inhibits growth of the MDR snd XDR strains of Mtb • Metabolomics efficacy of PRK is related to its ability to dysregulate arginine and proline metabolism, aromatic amino acid metabolism, purine metabolism and oxidative phosphorylation • Proteomic studies of Mtb infected mouse macrophages treated with PRK shows increase in autophagy and decrease in ROS and inflammation in macrophages • Thus, PRK compromises the pathogenic mechanism of Mtb by modulating a number of its virulence strategies in its host. • PRK is very effective in guinea pig. Orally administered PRK is more potent than even RIF and combination of RIF and PRK and HREZ+PRK are much more effective. • PRK has no toxic side effects on the treated animals • Overall PRK contributes positively to healing of infected lungs by mobilizing Arginase positive macrophages

Innovator: Indian Institute of Science Bangalore

USP: PRK clears Mtb in the lungs of guinea pig and mice at a clinically approved dosage and without any harmful side effects known.