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File Enrichment: The Way Out of Pharma's Productivity Crisis?

This article was originally published in Start Up

Executive Summary

To address the problem of attrition during lead compound discovery and early development, some large drug firms - Pfizer perhaps both the most vocal and committed -- are banking on file enrichment and selection. Better-informed compound library construction and more efficient lead selection could double the useful hit rate, they say, in effect doubling the number of successful new drug introductions downstream. There's room for combining empirical and rational approaches; for example, combining novel fragments to extend diversity with privileged fragments (or scaffolds) that reflect rational assumptions about drug motifs. For now, however, the proposition of file enrichment is much more theory than reality, until it is shown to actually reduce attrition both before and during clinical development, and so improve productivity.

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Plexxikon Inc.

Plexxikon begins the drug discovery process by identifying lead molecules that loosely fit those protein folds, or domains, that are conserved among druggable protein families. These molecular scaffolds may serve repeatedly as a template for designing new chemical entities against a variety of druggable targets within that family. As the number of scaffolds and structural information about them increases, the efficiency of selecting the appropriate one for a given drug target should improve, reducing the time from a hit to an optimized drug lead.

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