Anacor's eczema therapeutics: the Wankel rotary engines of dermatology

Anacor Pharmaceuticals, a company located near me in the Bay Area, has two interesting drug candidates in the pipeline to treat eczema. I've been meaning to review them for a while--at first I thought I needed to speak to someone at Anacor, but then I realized that a lot of the information is online and if I did manage to hear from an Anacor rep I'd probably only get a bland corporate response. (Ideally you want to hear criticism from a competitor to get the real dirt!)

The two compounds, AN2728 and AN2898, are also in clinical trials for treatment of psoriasis--the trials for psoriasis are a couple substages ahead of those for eczema. Look at the structures--you can see they are closely related compounds. They both inhibit the enzyme phosphodiesterase IV (PDE4). PDE4's job (it's primarily found in white blood cells) is to break a bond in a signaling molecule called cyclic AMP (cAMP).  Although cAMP participates in all kinds of processes in the body, in white blood cells it turns off inflammation. So if you inhibit the enzyme that breaks down cAMP, you inhibit inflammation.

So Anacor's compounds, which I believe are in trials as topical creams, could be an alternative to corticosteroids. Clinical trials in humans will show whether AN2728 and AN2898 have more or fewer side effects than steroids.

I find Anacor interesting because it's local, for me, and because boron compounds are chemically unusual in biology. Boron can form either three or four bonds with neighboring atoms, and while carbon can also do this (two single bonds and one double bond), Anacor says that using boron in their compounds lets them make molecules that can interact with enzymes in unusual ways that carbon compounds cannot.

A small contingent of medical chemists seems to be cheering Anacor on just because boron compounds are cool. It's like mechanics who love the Wankel rotary engine in the Mazda RX-7 because it works differently from engines in most other cars. But the ultimate test is whether these compounds work. It would be nice to have another topical option to reduce inflammation and itch.

Even if they do work, they'll only be treating the local symptom of the disease and not its cause or systemic origin. But, in their favor, that is how Protopic and Elidel work--when they DO work.