Abstract:
The present invention is directed to the discovery that pyrazinamide, a potent anti-tuberculosis agent acts through an entirely unexpected mechanism-through inhibition of the host enzyme poly ADP ribose polymerase (“PARP”). Thus, the present invention is directed to methods of treating: mycobacterial infections (Mycobacterium), especially M. tuberculosis using a PARP inhibitor, optionally in combination with at least one additional agent useful in the treatment of a mycobacterial infection, especially tuberculosis. Pharmaceutical compositions, especially including a pharmaceutical composition in oral or inhalation dosage form, comprising a inhibitor, optionally in combination with an additional anti-mycobacterial agent, especially an additional anti-tuberculosis agent represent additional embodiments of the present invention.
Abstract:
In one embodiment, the invention provides a method of treating a subject who suffers from a cancer (particularly a chemotherapeutic or radiotherapeutic-resistant cancer) or from an inflammatory disorder, the method comprising co-administering to the subject a pharmaceutically-effective amount of: (a) one or more elements or compounds selected from the group consisting of arsenic, an arsenite and arsenic trioxide (ATO); and optionally (b) at least one anticancer agent (preferably a DNA damaging agent); and/or (c) at least one or more Poly(ADP-ribose) polymerase (PARP) inhibitors other than arsenic, an arsenite and arsenic trioxide (ATO). In preferred embodiments, the arsenic for the treatment of cancer, arsenite and ATO serve as radio sensitizers for concomitant radiotherapy as well as PARP inhibitors. Methods for treating inflammatory disease are also disclosed. Related pharmaceutical formulations are also provided.