Keeping methyltransferases simple

BellBrook Labs and Reaction Biology collaborate on screening of methyltransferases for epigenetic drug discovery

Jeffrey Bouley
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FITCHBURG, Wis.—BellBrook Labs announced in mid-Septemberthat it was "undertaking a comprehensive effort" to validate purified humanmethyltransferases for robust, high-throughput screening-ready detection inBellBrook's recently developed Transcreener EPIGEN Methyltransferase Assay.
In this effort, the Madison-area company has been workingwith Malvern, Pa.-based Reaction Biology Corp., which is also the source ofthose purified human methyltransferases.
The team effort is aimed, the two companies say, "ataccelerating public and private drug discovery initiatives targeting theepigenetic modifications that underlie a broad range of diseases, includingcancer and autoimmune disorders."
The collaboration news was quickly followed by news at thebeginning of October that the two companies had combined the Transcreener HTSassay technology with Reaction Biology's purified enzymes to provide "acomplete methyltransferase assay solution for inhibitor high-throughputscreening and profiling."
Discovery of new drugs that target methyltransferases hasbecome a major initiative for many pharmaceutical and biotech companies becausethose enzymes are responsible for epigenetic modifications underlying a broadrange of diseases; however, efforts to identify new molecules that disrupt theactivity of aberrant methyltransferases have been slowed by the lack of robusthigh-throughput screening assays and high-quality, purified methyltransferaseenzymes, the companies note. Further complicating the situation is the factthat each methyltransferase in humans requires a specialized set of conditionsand components to produce activity.
"We launched the Transcreener EPIGEN back in September 2011,and a lot of customers and pharmas were evaluating it," recalls Robert Lowery,president and CEO of BellBrook Labs. "The assay worked great, but people havehad trouble working with the methyltransferase enzymes—the enzymes are verycomplicated and they are challenging to use with kinases. So to help ourcustomers, we pursued a strategy of looking at various commercial enzymes andwe found Reaction Biology's to be very high quality. We began to evaluatespecific enzymes of interest to make things easier for customers and that ledto the concept of packaging their enzymes with the EPIGEN to give people acomplete solution."
According to BellBrook, the Transcreener EPIGENMethyltransferase Assay has universal applicability across the entiremethyltransferase family. Meanwhile, Reaction Biology has produced more than 30recombinant human methyltransferases to what the companies both call "the moststringent purity and activity requirements in the industry."
What BellBrook then did was to undertake a comprehensiveeffort to identify the optimal reaction conditions for each of ReactionBiology's methlytransferases in the EPIGEN Methyltransferase Assay. By takingmuch of the guesswork and upfront assay development out of methyltransferasescreening and profiling, the companies say they had hoped their collaborativeeffort and resulting combined solution would accelerate the discovery of newdrugs for diseases with an epigenetic basis and reduce the cost of developingassays for such purposes.
In truth, Lowery notes, the decision to launch a combinedproduct line goes back to August, but the two companies wanted to make sureeverything worked properly before officially announcing that. The two companiesworked very well together, Lowery notes, and that led to a "flurry of activity"that resulted in a product line to announce just a couple months later.
"We found Reaction Biology to be really easy to work with,and they were open to the idea of collaborating and co-marketing right from thestart," he says. "They are mostly service and screening and profiling, andwe're making reagents, so there's really no competition between us and ourgoals align well. They do sell some products directly, but we will end up beinga good distribution channel for them. Reaction Biology is an outstandingpartner both from the scientific and business perspectives."

Jeffrey Bouley

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