DNA-Programmed Chemistry platform will be used to develop orally bioavailable, small molecule macrocyclic compounds.

Pfizer is teaming up with Ensemble Discovery to discover and develop drug candidates based on the latter’s Ensemblin™ technology. The collaboration, encompassing a number of pharmaceutical targets, will focus on protein-protein interactions.

Ensemble will receive an up-front payment and research funding. Pfizer retains the right to develop and commercialize any products arising from the collaboration in return for development milestones and sales royalties.

Ensemblins are a new class of orally bioavailable, small molecule macrocyclic compounds that Ensemble claims have the potential to behave like biologics and disrupt protein-protein interactions. Targets in such interactions are characterized by an extended binding motif, which is difficult to address using traditional drug design approaches, the company explains. In contrast, macrocycles have shown promise against such targets but have to date proven complicated to synthesize.

Ensemble is using its DNA-Programmed Chemistry (DPC) technology as well as conventional chemical synthesis for the creation and rapid assessment of large libraries of purified, synthetic macrocycle Ensemblins.

The company’s most advanced in-house Ensemblin program is focused on TNFα antagonists. It claims to have identified several series of selective and reversible small molecule Ensemblin macrocycles that competitively antagonize the activity of TNFα on TNF receptors in both biochemical and cell-based assays. They have demonstrated efficacy both intravenously and orally in an animal model of collagen-induced arthritis.

Ensemble signed an Ensemblin therapeutics alliance with Bristol-Myers Squibb in April 2009. In 2008, the company extended an alliance with Roche focused on using proprietary diagnostic assays based on the DPC technology in human clinical studies to analyze combinations of epidermal growth factor receptors in cancer tissues. The goal is to develop product prototypes that detect EGFR receptor dimers (protein complexes made up of two identical molecules) in human cancer tissue samples and ultimately to use those tests to improve the management of cancer patients and their therapy.

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