Wednesday, June 13, 2007

CombiUgi Says Order 2-Naphthyl Isocyanide

Two weeks ago I posted about the CombiUgi project, where I proposed that we make compounds from a combinatorial library predicted to have some potentially useful biological activity. The scientific blogosphere worked its magic and we now have a short list of compounds to make.

Rajarshi really worked hard on getting an algorithm to create the Ugi product SMILE codes and passed them through his tumor cell inhibition program. Out of about 68,000 he identified a shortlist of 21 that showed the most activity (see wiki for details). An example is shown below:



I find it very interesting that all the top hits involve 2-naphthyl isocyanide and over half involve boc-methionine. Is this real or even meaningful? We've been discussing these issues privately and I hope that Dan, Rajarshi and others continue the discussion openly.

In the meantime, we're ordering the chemicals and hopefully will have a few Ugi products to send to NCI for testing against their tumor cell lines.

The point of this excercise is not so much to prove that this model is correct or that we have found a new anti-tumor lead (though that would be nice) but that we can close the scientific loop of hypothesis-synthesis-assay in a completely open and collaborative scientific environment.

I welcome suggestions of other compounds from our virtual library that might be worth making (for any disease-related target), as long as we have assays that someone can run.

We are also working with Tony Williams to see if ChemSpider can serve as a database to store and manage the virtual library, the predicted properties and the assay results. Hopefully then we could increase the library to several million molecules.

Chemical Blogspace Tags

InChI=1/C11H7N/c1-12-11-7-6-9-4-2-3-5-10(9)8-11/h2-8H
2-naphthyl isocyanide

InChI=1/C5H11NO2S/c1-9-3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)
methionine

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