Drug designers now have a new tool in their arsenal that could easily boost the potencies of common drugs by up to 2,000 times.
On Monday, chemists at the University of Illinois, Urbana, partnered with researchers from the Big Pharma giants Bristol-Myers Squibb and Pfizer, published the results of a new study in Nature. The process of amplifying or improving a drug’s potency is called “methylation,” where individual hydrogen atoms on a molecule are replaced with single carbon atoms (that are, in turn, covered in hydrogen atoms).
The methyl additions kind of act like molecular spikes, which help anchor the molecule into its target receptor, cell, or protein, in turn boosting its potency. Chemists have known about improving drug design with methylation for decades, but it’s always a tricky process that often involves building the molecule from scratch with the methyl groups already included. Or, a series of new enzymes are needed to create a new drug, which is costly and time-consuming.
“If I want to work on a different molecule, I need a new enzyme,” Christina White, one of the study’s authors, told Science magazine. “We want [a reagent that is] just as selective, but general.”
Now, using this new “magic methylation” technique, chemists can simply replace specific hydrogens on a drug with methyl groups practically wherever they want on a molecule. To wax nerdy here, this new technique is akin to CRISPR-Cas9 in biotechnology, where a single chemistry tool can easily repair genes that previously required multiple, complicated, time-consuming, and costly steps.
To illustrate how useful methylation is, we can use a dreaded opioid drug as an example. Oxycodone, otherwise known as OxyContin, is basically morphine with an additional methyl group and some extra electrons. Codeine, an opioid painkiller often prescribed for controlling minor to moderate pain, is also just basically just morphine with an added methyl group. In this case, codeine is less addicting and less potent with the additional methyl, but its reduced potency makes it more versatile for treating pain in a greater number of patients.
Furthermore, increasing a drug’s potency could mean patients will require less of the drug for the same effect. That translates to less production costs on Big Pharma’s end, too. David Rees, the chief scientific officer at Astex Pharmaceuticals, told Science that, in regard to drug manufacturers, “Everyone will jump on this.”
According to the researchers, the “magic methyl” technique works for modifying at least 16 common drug molecule skeletons, meaning we could soon be seeing an entirely new generation of pharmaceutical drugs — and possibly even new “recreational” street drugs — created with this method.
Of course, as it always goes with new drugs, there are risks. Enhanced potency and modification isn’t always a good thing, and with a slew of new drugs could come a slew of new public health issues, too. Hey, at least we’ve got the trusty ol’ FDA watching our backs, eh? Welp.
