Programs to Facilitate Tuberculosis Drug Discovery: The Tuberculosis Antimicrobial Acquisition and Coordinating Facility

R. C. Goldman; B.E. Laughon; R. C. Reynolds; J. A. Secrist; J. A. Maddry; M.-A. Guie; A. C.Poffenberger; C. A. Kwong; S. Ananthan

Abstract

There is a real need to discover new drugs that are active on drug-resistant tuberculosis (TB), and for drugs that will shorten the time of therapy. Large pharmaceutical companies have traditionally led the quest for discovering and developing new antiinfective agents but this is not the case when it comes to diseases like tuberculosis that primarily occur in resource restricted countries. Throughout the world many research groups are actively engaged in the scientific discovery of new TB drugs. Unfortunately, most research laboratories do not have the necessary safety facilities or resources for all facets of TB drug discovery. The Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) was established in order to make comprehensive testing services available at no cost to research laboratories with an interest in discovering new TB drugs. The TAACF is a consortium of contracts managed and funded by the National Institute of Allergy and Infectious Diseases (National Institutes of Health, Bethesda, MD) as a resource to support preclinical drug discovery and development. The core of the TAACF is the Southern Research Institute, Birmingham, AL, which supports compound acquisition, storage, medicinal chemistry, and high throughput assays. Other collaborating groups provide biological data on antimycobacterial activity and cytotoxicity, preliminary in vivo toxicity, oral bioavailability and efficacy in animal models, specialty testing (such as activity against non-replicating persistent bacteria), and assistance in technology transfer for developing comprehensive promotional packages and facilitating partnerships with pharmaceutical companies for drug development. The TAACF program and recent progress that has been publicly disclosed by suppliers is reviewed. There are many aspects promising of the program that will not be discussed due to confidentially.

Keywords: Tuberculosis, drug discovery, Mycobacterium, screening