In Cancer Reserach, Finding a Valid Therapeutic Target is Only Half the Battle

[Guest guest]

[NIH to make 100,000 compounds available to researchers for screening

against targets.]

Combinational Chemistry for the rest of us

In pursuing therapies based on molecular differences between cancer

and normal cells, finding a validated target is less than half the

battle. The next step is to find a compound that can alter its

activity. In some instances the nature of the target suggests a

starting place - perhaps a peptide to interact with a binding domain,

or an ATP-analog for a kinase domain. But even here, and of course in

situations where there is no obvious candidate you have two broad

options: rational design based on structural data or screening a

library of compounds, armed with an assay. Since in many cases there

is no structural data for the target, and this is not always easy to

come by, screening for compounds is often the more accessible option.

But of course you first need a big and diverse library of compounds.

Now the NIH is developing a new initiative to make such libraries

widely available. This is excellent news for research groups that are

not already hooked into such resources. The NIH Molecular Libraries

Initiative (MLI) was recently introduced in an article in Science's

Policy Forum slot. As outlined there this initiative will create a

collection of over 100,000 compounds that will be shared between five

or six high-throughput screening centers that can be accessed by

investigators. These centers can also help optimize promising leads.

In addition the MLI plans to develop new libraries in neglected

regions of chemical space, help with assay design, develop new

instrumentation and even generate predictive algorithms to predict

how drugs might fare in absorption, distribution, metabolism and

excretion as well as toxicity.

Altogether, this new program promises to be a big shot in the arm for

molecularly targeted therapies. This is government science at its

best: putting the tools that only the biggest players have in the

hands of all scientists.