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Injectable prodrug of spectinamide as anti-tuberculosis agents (SJ-18-0007)

St. Jude Reference #SJ-18-0007

Description

Researchers at St. Jude developed a new injectable spectinamide prodrug, which will overcome spectinamide associated toxicity problems. The prodrug significantly improved the therapeutic window and demonstrated equal efficacy to parent spectianmides at the same dose and method of administration. This injectable prodrug can replace any injectable tuberculosis (TB) drugs in TB drug regimens to treat TB, including multidrug resistant and extensively drug resistant TB. The parent drug showed promising synergy and an improved therapeutic window with first line TB drugs in multiple murine models, e.g. rifampin and pyrazinamide.

Background: The dramatic rise in the prevalence of antibiotic resistance among bacteria requires the discovery and development of new antimicrobials to treat infections caused by these organisms. There is also a need for new therapeutic agents to treat biodefense pathogens.

Mycobacterium tuberculosis, which causes tuberculosis, remains one of the world's most deadly infectious diseases. As of 2007, the World Health Organization estimated that more than three million active cases of TB occurred worldwide annually leading to greater than one million deaths; with HIV infected individuals more prone to become infected with and develop the active form of TB. As the HIV pandemic has spread globally, it has correspondingly increased the number of TB cases. The currently recommend treatment for TB is lengthy, burdensome, and leads to non-compliance; which in turn increases multidrug resistant (MDR) and extensively drug resistant (XDR) strains for which are even tougher to treat.


 

Keywords

Injectable spectinamide prodrug, parenteral administration, toxicity, rifampin, pyrazinamide, antibiotic resistance, Methicillin resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus, multidrug resistant Streptococci pneumoniae, Neisseria gonorrhoeae, Mycobacterium tuberculosis, pan-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii. 


 

Granted Patents or Published Applications

International application WO/2020/097065 published May 14, 2020.


 

Related Scientific References


 

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Contact: chad.riggs@stjude.org

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