Protein small-molecule modulators

In chemogenomics and drug discovery, the most challenging task is to find small molecule modulators of protein function that specifically modulate the protein function of interest. Combinatorial chemistry has emerged as a powerful tool to address this problem by generation of large compound... 

Compound libraries as sources for small molecule modulators of protein function... 

Small molecules modulating microtubule assembly have played major roles as tools in microtubule research, in a manner closely related to their chemotherapeutic interest [1], Tubulin was first purified in the last century as the colchicine-binding protein proposed to be the subunit of cellular microtubules [2], More recently, a colchicine derivative was employed to help crystallization and determine the structure of tubulin by X-ray diffraction [3], The colchicine, vinblastine [4] and paclitaxel [5] sites are main drug binding sites of tubulin, to which many other substances bind. The discovery of microtubule stabilization by paclitaxel [6] prompted its clinical development [7] and a burst of research on new MSAs, as well as the generalized use of paclitaxel or docetaxel as convenient reagents to assemble (see Fig. 1), stabilize or detect microtubules in the laboratory. One example is the development... 

The choice of assay type in a drug discovery campaign is complicated. Are you seeking an agonist, an antagonist, or a selective modulator What tools (cell lines, recombinant proteins, small molecule probes, etc.) are at your disposal How many compounds do you want to profile What are your cost and time constraints Each of these issues can modify your determination of the optimal assay for your particular project. 

F. Civoli, J. Watson, An ultra-HTS process for the identification of small molecule modulators of orphan G-protein-coupled receptors, Drug Discov. Today 2003, 8, 785- 792. 

The Challenge to Make Small-Molecule Modulators of Protein Function... 

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