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CSU Process Flow Chart: In Vivo Evaluation of Anti-Mycobacterium tuberculosis Activity

Follow the flow chart to learn more about the assays used to screen the compounds for anti-TB activity. Links are provided for more thorough descriptions of the screening assays.

Blue text links are provided to downloadable documents and detailed descriptions of the procedures.

Go to detailed text description.

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Colorado State University (CSU) TAACF facilities are located in Fort Collins, CO and are led by Drs. Ian Orme and Anne Lenaerts. CSU performs in vivo and ex vivo testing as described below for compounds it receives from SRI. The purpose of this program is to provide a resource whereby new experimental compounds can be tested for their capacity to inhibit the growth of virulent M. tuberculosis in a realistic in vivo aerosol mouse function model. After each test is complete, results are returned to SRI for ultimate delivery to the compound suppliers.
CSU active flowchart
RTI link to description of services
 
Compounds received by CSU
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Determination of max tolerated dose (MTD)- Min. compound requirement:84 mgMinimum compound requirements: 84 mgarrow down
arrow down to GKO Knock-out model on leftarrow down to Murine Aerosolized model right
Animal model studies: Murine Gamma Knock-out (GKO) model (Minimum compound requirements: 300 mg)--Murine Aerosolized TB Model--(Minimum compound requirements: 900 mg.) Then data retured to SRI and report sent to supplier.Link to Murine Gamma Knock-out descriptionLink to Murine Aerolized TB model description
arrow down from GKO to centerArrow down from Murine model to center
Date returned to SRI and report sent to supplier
Arrow down to decision diamond
TAACF medical chemists review the data and consider commercial development Requirements for moving to commercial development: log10 protection, factor >= 0.3
 Unsuccessful med chem review = no further evaluation; report to supplier
Successful med chem review= report to supplier and proceed
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NIAID alerted about compound potential.Link to RTI description
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