Thursday, August 02, 2007

First NCI Results

We just got the first results from the National Cancer Institute's testing of one of our Ugi products (UC0204) for activity again tumor cell lines. It looks like there was no significant activity, which is not unexpected since these molecules were not selected based on any tumor related criteria.

In the future, we will be sending over compounds from the CombiUgi project that score higher on Rajarshi's algorithm to predict anti-tumor activity and things should get more interesting.

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At 12:24 AM, Blogger Bill Hooker said...

How amenable are SMILES to text-based combinatorial approaches? Could one auto-generate a zillion SMILES, each of them a real(istic) molecule, and then auto-submit those to Rajarshi's algorithm?

At 8:40 AM, Blogger Unknown said...

Definitely not a candidate for full 5-dose testing. It will be interesting to see how compounds that are predicted to be active fare.

A note on the data presentation. A lot of people are having trouble understanding the graph at first. Any suggestions about how we could improve things would be appreciated. First, the number reported kind of looks like simple % of control, but it isn't quite. We take into account the number of cells at the start of the experiment. So the basic procedure is
1) plate cells
2)24 hours later, add compound.
also at 24 hours, count cells in sample of control plates (TZ)
3)48 hours after that, count cells in control (TC) and drug (TD) plates.
If TD > TZ then the growth % is
100*(TD - TZ)/(TC-TZ)
If TD < TZ, that is the compound killed off cells that were there to start the experiment, then the growth % is
So positive numbers are % of control growth during the 2 day exposure and negative numbers are % original cells killed.

The graph averages all the values for each cell line and that becomes the center line for the graph. Bars that point to the right of the center line are cell lines with more inhibitory response than the average for this compound and bars that point to the left are less inhibited than average. Don't ask me why that is the convention, it started before I got here.

One last fact. The criterion for going on the a five dose test is that at least 9 cell lines have a growth percent of 60 or less. This compound only had one cell line with 60 or less.

At 8:48 AM, Blogger Jean-Claude Bradley said...

Yes that is the point. Rajarshi has also created a web service that generates up to 2 million Ugi products that we can make from reasonably cheap starting materials very quickly in our lab.
SMILES in and SMILES out.

At 8:50 AM, Blogger Jean-Claude Bradley said...

Thanks - we were wondering how to interpret the results. We'll see if the compounds predicted to be active really are...

At 1:24 PM, Blogger Rajarshi said...

Bill, playing with SMILES from a text processing point view is very easy. More so, if the input SMILES are in a 'standard' form (such as the replacement group always being on the left etc).

My virtual library generating web service provides little more sophistication but really it ends up just looping over the fragments and stitching them together to give the final molecules


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