“The drug discovery world has always been looking at natural products as a valuable source of bioactive molecules,” said Dmitry Genis, Ph.D., CEO, Asinex.
“It is remarkable to note that 33 percent of new chemical entities discovered between 1981 and 2002 are natural products (or related to them). However, natural product chemistry is challenging and biologists have to deal with complicated screening procedures.
“Since the 1980s most pharmaceutical companies have reduced their efforts in this area, and the advent of synthetic combinatorial chemistry has further contributed to this decline.”
Dr. Genis reported that times are changing. “The past two decades of high-throughput screening have shown that the random generation of compound libraries by a pure combinatorial chemistry approach has created millions of molecules that did not match the requirements of the drug discovery industry. Therefore, it makes sense to use natural product structures as starting points for new drug-like libraries.
“Natural products represent an additional source of diversity that cannot be found in synthetic combinatorial libraries. Our BioCore approach is a synergic compromise that solves the problematic issues of natural products and combinatorial libraries and, at the same time, allows the unification of the positive features of these two areas.
“BioCore is the key component of our BioDesign approach. The idea is to create compounds that contain highly privileged elements from natural products and known drugs. A BioCore is the combination of two heterocycles—one is aromatic and one is saturated, linked by a carbon-carbon spacer fragment. We strongly believe that following the BioCore framework allows chemists to create nature/lead-like scaffolds,” explained Dr. Genis.
Although the idea of incorporating natural product elements is not novel, the company has identified what it feels are under-represented areas of chemical space and implemented those into real libraries. Dr. Genis reports that, “Based on the BioDesign approach, we offer research tools based on bio-building blocks, bio-fragments, and lead-like sets, enabling easy hit-to-lead follow-up.”
As more medicinal and computational chemists incorporate fragment-based approaches into their discovery toolbox, the field is expected to make further progress in accelerating the pace of drug discovery.