The aim of this work is develop a novel protein synthesis inhibitor for the treatment of TB. The starting point of the collaboration with Anacor Pharmaceuticals were inhibitors that demonstrated proof of concept on-target activity and good in vitro activity against M. tuberculosis. We have found that modifications to the structure of a Gram-negative LeuRS inhibitor, which is efficacious in humans, give rise to more potent inhibitors that are preferentially active on M. tuberculosis. Work on several advanced leads

The novel aminobenzimidazole, VXc-486, which targets gyrase B, potently inhibits multiple drug-sensitive isolates and drug-resistant isolates of Mycobacterium tuberculosis in vitro (MICs of 0.03 to 0.30 ug/ml and 0.08 to 5.48 ug/ml, respectively) and reduces mycobacterial burdens in lungs of infected mice in

Clofazimine, one of the riminophenazine class drugs, is effective in treating the mycobacterial infection Hansen’s disease (also known as leprosy). Clofazimine and other compounds of this class demonstrate impressive bactericidal and sterilizing efficacy against TB in vitro and in mouse models of the disease. Although its efficacy against TB is promising, clofazimine has poor solubility and a bright red color, its extremely long half-life leading to high accumulation of the drug in tissues of patients with consequent side effects including pronounced skin discoloration.

Tryptanthrin is a natural product of a Chinese/Taiwanese medicinal plant. This compound and its relatives (collectively known as the tryptanthrins) have been extensively explored as anti-bacterial, anti-malarial and anti-cancer agents. During the 1990s, tryptanthrins emerged as potential anti-tuberculosis therapeutics with the ability to prevent growth of both drug sensitive and drug resistant tuberculosis bacteria. However, due to the inability of the particular compounds tested to kill bacteria in mouse models of TB, tryptanthrins were not pursued.

Quinolones are one of the few classes of antimicrobial agents that are totally synthetic in origin. The first quinolone, nalidixic acid, was introduced in the 1960s as a narrow-spectrum agent used primarily for the treatment of urinary tract infections. Quinolones possess many desirable attributes for a first-line therapeutic agent against TB. These include potent bactericidal activity against both replicating and non-replicating Mycobacterium tuberculosis (M.tb), favorable long-term safety indicators, oral bioavailability, and an ability to penetrate macrophages.