So much to do, so little time

Trying to squeeze sense out of chemical data

Archive for the ‘chemistry’ Category

Kinase Inhibitors and Polypharmacology

without comments

The Curious Wavefunction has a nice post on the issue of selective and non-selective kinase inhibitors. An interesting commentary, especially in the light of the recent paper on network polypharmcology. While there have been a number of papers on polypharmcology and the idea itself is very attractive, it has seemed to me that for this approach to succeed we need very detailed information on the targets and systems involved in these networks. Indeed, a current project of mine is currently hitting this problem. As Ashutosh notes,

… in the first place we don’t even know what specific subset of kinases to hit for treating a particular disease. First comes target validation, then modulation.

Written by Rajarshi Guha

November 5th, 2008 at 11:18 pm

Combinatorial Libraries and Mixtures

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Houghten, R. et al, “Strategies for the Use of Mixture-Based Synthetic Combinatorial Libraries: Scaffold Ranking, Direct Testing In Vivo, and Enhanced Deconvolution by Computational Methods”, J. Comb. Chem., 2008, 10, 3-19

Recently a collaborator pointed me to the above article by Houghten and co-workers where they describe the use of mixture-based combinatorial libraries for high-throughput screening (HTS) experiments.

Traditionally an HTS experiment will screen thousands to millions of individual molecules. Obviously, it’s all done by robots so though you have to be careful during setup it’s not like you have to do it all by hand. But the fact is, if it’s possible to reduce the actual number of individual screens, life becomes easier and cheaper. Houghten et al describe an elegant approach that does just this.

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Written by Rajarshi Guha

August 31st, 2008 at 8:12 pm