contain fluorine atoms, according to SciFluor. The highly reactive element forms intensely strong bonds with the carbon atoms in proteins and other biological molecules. SciFluor chemists use this property of fluorine to slow the breakdown of their modified drugs by enzymes in the liver, Askew says. This increases the drug’s life span in the body, and may allow patients to take lower doses, he says.
Other startups are pursuing similar strategies. Auspex Pharmaceuticals in San Diego, CA, strengthens chemical bonds by replacing hydrogen atoms with deuterium, a heavier isotope of hydrogen. The stable, naturally occurring variant of hydrogen is embedded in Auspex’s lead drug candidate SD-809, which is similar to the approved drug tetrabenazine (Xenazine). Tetrabenazine is marketed by the Danish firm Lundbeck as a treatment for the involuntary movements associated with Huntington’s disease and other disorders.
Auspex is hoping that SD-809 can be used at lower doses than tetrabenazine because its stronger bonds will protect it from breakdown in the body.
SciFluor uses fluorine rather than deuterium to modify drugs because the fluorine-carbon bond is much stronger than the deuterium-carbon bond, Askew says. Chemists have incorporated at most about seven fluorine atoms into their drugs, he says.
“We wouldn’t propose making a drug molecule with every hydrogen replaced by fluorine,” Askew says. “It would be Teflon.”
Fluorine has another useful characteristic: it eases a drug’s ability to mix in with fatty compounds called lipids, which are key ingredients in cell membranes. SciFluor is taking advantage of this property to make drugs that can penetrate into the brain by getting past the blood-brain barrier.
Hiller says his researchers have used fluorine modification to create eight new chemical entities based on drugs used against cardiovascular disorders, nervous system diseases, and cancer.
One of the new SciFluor compounds is an analog of ezogabine (Potiga), an epilepsy medication developed by Valeant Pharmaceuticals North America of Durham, NC, and distributed by GlaxoSmithKline of Research Triangle Park, NC.
Ezogabine was the first epilepsy drug designed to work by influencing cell structures called neuronal potassium channels, which are believed to regulate nerve signals. The drug’s side effects can include changes in heart rhythm and an inability to fully empty the bladder. Hiller says SciFluor’s redesigned version of the drug addresses both of those side effects, and two others.
The company is in discussions with a number of companies about potential partnerships, Hiller says. SciFluor’s scientists are using innovations in fluorine chemistry not only from Harvard, but also from the Scripps Research Institute in La Jolla, CA, the University of Michigan at Ann Arbor, and other research centers.
“Fluorine is becoming one of the most important ways of evolving molecules,” Hiller says.
