Clofazamine is a drug from the riminophenazine class that was developed in the 1950s for use against leprosy, but which has also shown activity against M.tb. However, riminophenazines have also been known to produce a particularly problematic side effect—skin discoloration—which could further the stigma already associated with TB. Since 2007, the TB Alliance has been working with the Institute of Materia Medica, Chinese Academy of Medical Sciences, and the Beijing Thoracic Tumor and Tuberculosis Research Institute to discover improved next-generation riminophenazines. Data will show that the partners are finding new promise in this old compound class as a component of shorter, faster-acting novel regimens.
Since 2007, the TB Alliance has been working with the Institute of Materia Medica (IMM), Chinese Academy of Medical Sciences, and the Beijing Thoracic Tumor and Tuberculosis Research Institute (BTTTRI) to discover and develop next-generation riminophenazines with improved pharmacokinetics and fewer side effects. During this time, IMM, in collaboration with the TB Alliance, has designed and synthesized close to 1,000 riminophenazine analogs, leading to the identification of a short list of anti-TB compounds that have been shown to be potent, safe, and stable, and demonstrate efficacy in murine models of M. tuberculosis infection. Through this collaboration, our partners, supported by Chinese government grants, have worked with Shanghai Institute of Materia Medica (SIMM) and the National Institute for the Control of Pharmaceutical and Biological Products (NICPBP), bringing further resources and enabling the conduct of pharmacokinetic and safety studies. Further excitement around this chemical class is based on its potency and synergy as identified through the pre-clinical drug combination studies. Work on this project continues with the expectation of producing a lead candidate for preclinical development in 2012. With continued success, a pivotal building block for future novel TB regimens could be on the horizon.