About Macrolides

macrolides Cempra has exclusive worldwide rights from Optimer Pharmaceuticals to discover, develop and commercialize macrolides from a library of more than 500 compounds. Using the licensed patented technology, Cempra is able to incorporate different sugar motifs into the macrolide ring, thus creating the next generation of macrolide drug candidates.

Macrolide antibiotics are characterized by a macrocyclic ketone ring and two sugar rings at the 3 and 5 positions of the macrocyclic ring. The macrocyclic ring was modified to create clarithromycin (Biaxin©) and azithromycin (Zithromax©) with improved pharmacokinetic properties. For telithromycin (Ketek®), the sugar at the 3-position was removed and replaced with a keto group - hence the class name of ketolides - and an additional modification allowed for binding to a secondary site on the bacterial ribosome, resulting in enhanced activity against resistant strains.

A desosamine ring at position 5 is present in all macrolides/ketolides. This ring (labeled "Open for Discovery" in the Figure above) contains the N-dimethyl group that is required for binding to the bacterial ribosome, resulting in the inhibition of protein synthesis.

Using aglycon semi-synthetic chemistry technology, Cempra is able to remove the desosamine ring to permit large scale preparation of a "naked" macrolide ring that can be modified at the 5-position with any other side chain or ring. For the first time since the discovery of erythromycin, it is possible to make hundreds of macrolide derivatives - and some of these compounds show superior activity.

Cempra's lead clinical macrolide, solithromycin, is a highly potent next-generation macrolide of the fluoroketolide class, with activity against macrolide-resistant pathogens which was derived from this program.