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Structure Work Unveils a New Apoptosis Drug Target

This article was originally published in Start Up

Executive Summary

In 1997, Abbott Lab's Steve Fesik showed how a complex between a survival protein and a cell death-inducing helix interacted, triggering a spate of apoptosis-oriented (programmed cell death) cancer research. Now a research team has identified a distinct and completely unforeseen site on a death protein that activates its cell-killing function, potentially kicking off a renaissance in this still challenging field.

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Aileron Therapeutics Inc.

Aileron Therapeutics engineers peptides that contain spiral confirmations called alpha helixes. These spirals are often unstable and fall out of shape--at least when manufactured in the lab. By placing a hydrocarbon staple between the turns in the spiral, Aileron's technology enables peptides to retain their stable conformation, and to arrive at their target destinations in active form. Many of the proteins involved in disease contain these alpha helix structures, and the ability to reproduce synthetic mimics would open up a multitude of therapeutic doors.

A New, Compelling Reason to Target Hsp90 in Tumor Cells

The finding that hsp90, a "molecular chaperone" that shuttles proteins throughout cells and performs a critical role in the mitochondria of tumor cells could have a profound influence on the development of an emerging class of drugs. It may help explain the limited effectiveness of current hsp90 inhibitors, which do not get into the mitochondria. The authors of the paper describing the work show that an hsp90 inhibitor that does get into the mitochondria has profound cell-killing capabilities.

Idun the Latest to Seek Shelter via Pfizer's M&A Highway

In February, Idun Pharmaceuticals became the fourth company acquired by Pfizer in the last 15 months. While those transactions reflect different mixes of product and technology breadth, they suggest a greater alignment between the interests of some private biotechs, their investors, and potential pharma company acquirers, as well as an evolution in the deal calculus for choosing M&A over an alliance or IPO.

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