Acne-Fighting Boron Compounds, Anacor, and Medicis
Today biopharmaceutical company Anacor announced a partnership with Medicis to discover and develop small molecules to fight acne. Medicis brings its expertise in dermatology and aesthetics treatments to the table (it's the company behind Juvederm, an injectable wrinkle filler). Meanwhile, Anacor's mission is developing boron-containing drugs.
Now, you don't see boron in drugs very often. The first boron-containing drug- Millenium's Velcade, for multiple myeloma- was approved less than ten years ago. Derek Lowe has mused about why medicinal chemists may have been reticent to check out boron compounds.
But Anacor has built its company on boron chemistry. From its website:
Two Anacor compounds in clinical development (Source: RSC)
Boron based compounds have a unique geometry that allows them to have two distinct shapes, giving boron based drugs the ability to interact with biological targets in novel ways and can address targets not amenable to intervention by traditional carbon based compounds.
So what's this mean, exactly? It goes back to general chemistry. Boron has unusual bonding properties. Its outer electron shell, the most important one for chemical bonding, has only three electrons. If it makes three bonds to other atoms, it then has three pairs of electrons in its outer shell. That's one pair short of what chemists typically consider stable. Still, these electron-deficient boron compounds tend to be pretty stable anyway. They have a flat shape to them chemists call trigonal planar.
But these flat boron compounds have the potential to take in two more electrons. When they come into contact with, say, an oxygen or nitrogen-containing compound rich in electrons, the boron compound forms a new bond, called a dative or coordinate covalent bond. And the molecule changes its shape from flat (trigonal planar) to tetrahedral. Those are the two distinct shapes Anacor is talking about. And the company has made a few chemical tweaks to control this type of boron reactivity.
What's this have to do with acne? Well, the entire story's not exactly clear. But we do know that enzymes often use electron rich oxygen, nitrogen, and sulfur motifs to do their business. And we know that Anacor's antifungal in clinical trials, AN2690, gums up protein production with its distinctive bonding properties.
We also know acne isn't a completely new area for Anacor. At a 2006 American Academy of Dermatology Conference Anacor presented a compound designed to kill Propionibacterium acnes, a rod-shaped bacterium linked to zits. These bacteria normally dwell on human skin but clogged pores swell their ranks, and the chemicals they secrete (like propionic acid, hence their name) lead to the inflammation and irritation typical of acne.
Antibacterials are already a common acne treatment. But the press release announcing the partnership doesn't say whether the Anacor/Medicis acne target has to do with bacteria. We'll surely hear more as the partnership progresses.
More reading: WebMD acne center
Boron-containing inhibitors of synthetases. Chem. Soc. Rev. DOI: 10.1039/c0cs00131g
Boron compounds can have two distinct shapes. (Source: RSC)