2The Nucleus April 2012
HepatoChem (http://www.hepatochem.com/)is a company co-found-ed in 2008 by MarcBazin, formerly of Pfizer, and Professor John T. Groves, holder of the Hugh Stott Taylor Chair of Chemistry atPrinceton University.HepatoChem was startedin the Groves lab atPrinceton, but in August2011 moved to theBiotech InnoVentureCenter in Beverly, MA.My interest in Hepa-toChem was piqued byBusiness Development Manager Shelly Amster at a recent NESACS Monthly Meeting. A subsequent interview wasarranged with HepatoChem President, Marc Bazin, at their Beverly facility.HepatoChem uses technology based on many years of metalloporphyrin research conducted at Princeton in theGroves laboratory. A variety of metalloporphyrins (Fig. 1)areused to simulate liver metabolism and oxidatively con-vert drug candidates
to metabolites in milligram togram quantities. This is in stark contrast to the nanogramquantities available by
biological methods.Easy access to large quantities of metabolites allows struc-ture determination and additional evaluation and testing,which would not be possible without the larger quantitiesavailable from HepatoChem’s
methods. “Thetechnology we developed at HepatoChem can produce notonly metabolites but also new analogues of lead candidatesthat could have better biological properties than the originaldrug. This positions it as an important tool for drug discov-ery.”Initial screening is done in 96-well plates loaded withthe test molecule. A series of test reactions are then con-ducted in which the metalloporphyrin, the oxidant, and thesolvent are varied. These experiments are then analyzed byLC-MSMS to identify a profile of metabolites and allowsrapid selection of conditions to produce the targetedmetabolite. (Fig 2) A second round of experiments allowsoptimization and larger scale production of any or all of themetabolites generated in the screen.Examples of reactions which can be achieved with met-alloporphyrin oxidation are hydroxylation, imine and enam-ine formation, halogenation, carbene insertion, amineformation and dealkylation. Tolbutamide is an examplewhich illustrates aliphatic hydroxylation and dealkylation(Fig 3).HepatoChem has also partnered with Princeton-based Novatia, http://www.enovatia.com/, a capillary NMR con-tract laboratory, to do structure elucidation of metaboliteswith small amounts of material (0.1-0.5 mg).Although only a four-person company at this stage,HepatoChem already has numerous clients ranging fromstart-ups to big Pharma. “Our clients are very satisfied withthe quality and speed of our service.” Dr. Bazin stated thatthe business in liver metabolites is $100 million per year and their business is expected to grow rapidly for a number of years. “This is very exciting to see our company growingin this economy.”
Synthetic Liver Metabolites
An interview with HepatoChem President, Marc Bazin
By Michael P. Filosa
President Marc Bazin (r) and Project manager Ryan Buzdygon photographed in HepatoChem’s Beverly laboratory.
Metabolites formed by biomimetic oxidation of Tolbutamide.
Graphical illustration of metabolites formed by theoxidation of aminopyrine with HepatoChem’s technology.
A Synthetic Metalloporphyrin