The Biomimetic Alternative

Biomimetic Chemistry:
An Alternative to Microsomal Metabolite Synthesis

In recent years, drug developers have grown to rely on the use of microsomes for drug metabolite production. Microsomes contain the native concentration of different cytochrome P450 enzymes found in the human liver and generate metabolites of parent drug compounds. While microsomes have proven valuable as a predictive tool, their productive capabilities are limited. Biomimetic Chemistry, on the other hand, possesses the advantages of both chemistry and biology and is thus a much more efficient tool for metabolite synthesis. In fact, with biomimetic chemistry, large scale metabolite generation is enabled in one step by mimicking and optimizing the same biotransformation reactions that occur in the liver.

Comparison of Biomimetic Chemistry vs Microsomal Metabolite Synthesis



Microsomal reactions are run at very dilute concentrations (uM of substrate). Consequently, large volumes of microsomes are needed to produce metabolites at significant scale. This means that accessing sufficient quantities of metabolites for various tests (bioactivity, toxicity, etc.) is prohibitively expensive.

Biomimetic Chemistry

Because biomimetic chemistry utilizes organic solvents, the reactions can be run at much higher concentrations than that of microsomal incubations. This enables large scale synthesis (mg to gram quantities).



There is no simple way to significantly increase the yield of a desired metabolite using microsomes. Methods involving genetic modification of the appropriate enzymes for example take years to perform.

Biomimetic Chemistry

By contrast, biomimetic chemistry is a chemical process in which optimization can be performed by modifying the combination of reagents and catalysts as well as the temperature which produce a desired metabolite.



The microsomal incubation contains a crude mixture of buffers, salts, enzymes, fats, etc., all of which need to be removed in order to isolate and begin purification of the desired metabolite. Large incubation volumes (several liters of water and buffers) make this removal process time-consuming and labor intensive. In addition, recovery is lowered since the precipitation of proteins can trap the metabolite.

Biomimetic Chemistry

In comparison to the microsomal incubation media, the biomimetic reaction condition is more concentrated, thus enabling an easier sample work-up. (In fact, the concentration is 1000X that of the microsomal incubation.) Further, there is no precipitation of proteins because there are no proteins involved in the process. The use of organic solvent in the reaction also simplifies the work-up.



Using microsomes, there is no way to bias for production of minor metabolites. Thus, attempts to generate a metabolite that is naturally produced in small quantities will prove challenging, time-consuming, and wasteful. Further, microsomal metabolites may not be the observed metabolite in blood, serum, urine, etc. in vivo. In such cases, metabolite synthesis through this technology can prove impossible.

Biomimetic Chemistry

Using a diverse panel of organometallic catalysts and oxidants, oxidation should occur comprehensively at all of the reactive positions in the molecule. Thus, significant quantities of a metabolite can be produced regardless of whether it is the major or minor metabolite in vivo. And while microsomal technology often fails to identify and produce metabolites found in blood, serum, urine, etc. in vivo, isolation of metabolites found outside the liver is enabled with biomimetic chemistry.



Liver microsomes, together with the relevant buffers and reagents necessary for metabolite synthesis, routinely cost upwards of $5,000 to $10,000.

Biomimetic Chemistry

The BMO kit however is a fraction of that cost (several hundred dollars).



Metabolite production with microsomes can take several weeks.

Biomimetic Chemistry

Using the simple, three-step method (screening, optimization, and production), metabolite synthesis can be achieved in a few days.

Given the limitations of microsomal technology, drug developers often postpone metabolite synthesis until the later stages of the development process. Unfortunately, putting off metabolite synthesis (and the associated metabolite tests) comes with huge risks and unforeseen consequences. Oftentimes, drugs that ultimately fail to pass the later phases of the FDA approval process due to, among other things, drug toxicity, are pushed along in the pipeline. With early knowledge of lead drug candidate metabolites, drugmakers can drastically improve the quality of their pipeline and ultimately save millions.

Metabolite Synthesis

Through our revolutionary technology, HepatoChem enables cost effective testable quantities of metabolites in-house even at the earliest stages of drug discovery. This new capability, which enables affordable early metabolite toxicity testing, offers drug companies the opportunity to save millions each year through dramatically improved drug pipelines.

Metabolite Production Services

Our unique approach to Metabolite Synthesis has been trusted for over a decade by some of the largest pharmaceutical companies in the world.

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