Adefovir (Acting like adenosine)
1st June 2006
Many people who come here from Gilead seem to peek at the Tamiflu page and take off. Gilead, you see, are actually the people who came up with Tamiflu, not Roche. They simply purchased the rights. After the whole bird flu thing pushed it into the public eye, Gilead and Roche had a brief spat, which was settled a few months later.
In general, this is the sort of thing Gilead make: small molecule antivirals. Let’s take a look at another Gilead drug, adefovir:
Shown along with it are adenosine and deoxyadenosine, the compounds that we represent with “A’s” in listings of RNA and DNA sequences, respectively. Many viruses, Hep B and HIV among them, are composed of RNA (as opposed to the more familiar DNA in your cells). Normally, DNA is transcribed into RNA, and not the other way around. In the case of the viruses, they encode a special enzyme, reverse transcriptase, which can “reverse transcribe” RNA into DNA. This is unique to retroviruses and is, of course, a drug target.
Adefovir, as you’ve no doubt figured out, is a mimic for adenosine nucleotides and targets reverse transcriptase. The most familiar example of the nucleoside/nucleotide-mimetic class to you is probably AZT, which is a thymine nucleoside mimic (nucleosides have a ribose and a base, nucleotides have all that and a phosphate group).
If monkeying with the letters that comprise the genomic book sounds a bit dangerous, it is. It is an analagous strategy to much of cancer chemotherapy, and specifically targeting HIV has proven hard. While their toxicity profiles continue to improve, antivirals like this tend to have more lavish toxicity than many other drugs. The trickiness arises from the fact that viruses aren’t neat self-contained packages with their own unique metabolisms to attack (like bacteria). This makes it much easier for them to hide, obviously. Unfortunately, this likely means that viral infections will always be harder to treat than bacterial ones.
Adefovir, for example, was originally intended for HIV therapy. The dose levels needed, however, caused kidney problems. At lower doses it is still effective against HBV (Hep B) and much less nephrotoxic, so that’s what it’s used for today. Tricky business, these wonder drugs.
Night!