Nature undervalued in drug discovery

By Mike Nagle

- Last updated on GMT

Related tags: Drug discovery, Us food and drug administration

Mother nature still has the jump on major pharma firms when it
comes to designing therapeutic products, a new study suggests.

David Newman and Gordon Cragg from the US National Cancer Institute have analysed all of the new chemical entity (NCE) drugs approved by the US Food and Drug Administration in the last 25 years. Perhaps surprisingly, of the 1184 drugs released, only 30 per cent were deemed synthetic in origin. The others were all obtained from natural sources or chemically designed to mimic natural products, despite few major pharma firms specifically dedicating resources in this area. NCEs are totally new drugs that have never been released before, as opposed to modified versions of existing treatments - sometimes called 'me-too' drugs. As R&D costs in the pharma industry skyrocket, the number of NCEs has been declining, reflecting a reduction in productivity and innovation. The study suggests that if pharma invested more in drug development programmes inspired by natural products, perhaps this trend could be halted. "Fortunately, however, research...is continuing the modification of active natural product skeletons as leads to novel agents, so in due course, the numbers of materials developed by linking Mother Nature to combinatorial synthetic techniques should increase,"​ said the researchers in an article scheduled for the 23 March edition of the Journal of Natural Products. Despite the pharma industry continually developing more advanced drug development technologies, natural products are still involved in around 50 per cent of small molecule drug development in the last six years, according to the report. "We strongly advocate expanding, not decreasing, the exploration of Nature as a source of novel active ingredients that may serve as the leads and scaffolds for elaboration into desperately needed efficacious drugs for a multitude of disease indications,"​ said Newman and Cragg. Combinatorial chemistry is estimated to be used in around 70 per cent of drug development programmes since 1981, has only resulted in a single drug designed from scratch, according to the study. Although the authors admit that combinatorial chemistry techniques are without par for optimising drug candidates, the emergence of only one de novo​ drug perhaps highlights its relative weakness in this area. The drug the authors are referring to is Onyx's Nexavar (sorafenib), which was developed in conjunction with Bayer. The compound inhibits multiple kinases to prevent crucial tumour and blood vessel growth processes. Despite the drug being approved for kidney cancer, it recently failed a Phase III trial in melanoma. The only other multiple kinase inhibitors approved are Pfizer's Sutent (sunitinib), which was approved for use against advanced renal cancer and gastrointestinal stromal tumour within a month of Nexavar, and GlaxoSmithKline's Tykerb (lapatinib), approved last week as a breast cancer therapy. Taxol (paclitaxel) remains a popular drug to treat breast cancer (and also lung and ovarian cancers). The drug was first isolated from the bark of the Pacific yew tree and is just one example of successful drugs from natural sources.

Related topics: Preclinical Research

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