That Darned Nail Fungus

Example of a fungal nail infection (Randen Pederson)

People don’t like having nail fungus. Although most insurance plans do not cover treatment (except in cases where other conditions exist that may lead to complications), there is still plenty of money to be made in providing a means for getting rid of it.

Pharmaceutical company Merck & Co. invested in a new topical treatment (dubbed AN2690) belonging to a smaller company called Anacor. Apparently Merck has been slow to develop it further so now Anacor is taking back complete control, while looking for other more helpful partners. According to Merck returning nail fungus drug to Anacor:

Drug giant Merck & Co. will return development and commercialization rights of a topical anti-fungal treatment to Anacor Pharmaceuticals Inc.

Palo Alto-based Anacor had played up its three-year-old partnership with Merck subsidiary Schering, which was responsible for a Phase III trial of AN-2690 to treat a nail and nail bed infection called onychomycosis. But Schering and Merck, which bought Schering last year, had delayed trial enrollment for more than a year.

Perhaps Merck decided it wasn’t so promising after all. That, or their number crunchers determined there are bigger gains to be had by focusing on other drugs first. Although the Anacor CEO has tried to put a positive spin on it, it looks like Merck has basically dumped Anacor.

Anacor Boron Technology

Boron is has an atomic number of 5 in the periodic table

Anacor is into boron-based small molecule therapeutics and indeed AN2690 contains boron as critical element. According to the AN2690 profile at the company website:

AN2690 has a novel mechanism of action that targets an essential protein synthesis enzyme, leucyl-transfer RNA synthetase, or LeuRS. This enzyme plays a pivotal role in fungal protein synthesis by attaching the leucine amino acid to transfer RNA, or tRNA. In addition, LeuRS also plays a key role in ensuring the correct synthesis of leucyl-transfer RNA. Our research has demonstrated that compounds that bind to the specific site on LeuRS involved in the synthesis of leucyl-transfer RNA also inhibit the attachment of leucine to tRNA, resulting in the inactivation of LeuRS and inhibiting protein synthesis within the fungal cell. The inhibition of protein synthesis leads to termination of cell growth or cell death, eliminating the fungal infection. We have shown that this inhibitory activity requires the presence of boron within the compound, as the replacement of the boron atom in AN2690 with a carbon atom inactivated the molecule.

According to Damian Krysan, assistant professor of Pediatrics at the University of Rochester Medical Center ,“We don’t have vaccines against fungal infections and the few drugs we do have aren’t always effective. We’ve got a lot more work to do to figure out whether tamoxifen could be used in high doses or whether it could be used in combination with other treatments, but we’re excited about the possibility of giving doctors another way to help these critically ill patients.”