Approach

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  • Clc chloride ion channel, this is a key target class for the company’s i-QUEST discovery programmes Clc chloride ion channel, this is a key target class for the company’s i-QUEST discovery programmes

Nemgenix’s crop protection efforts are focussed on developing novel, safe nematicides.

The established nematicide market is estimated at around US$1bn pa. Although an enormous spend, the potential size of the market is thought to be several billion dollars pa. The failure to reach this potential is primarily due to a combination of the progressive phasing out of many of the front line nematicides due to their toxicity and environmental impact and the failure of the agrochemical industry to develop safer replacements with broad application.

One of the reasons why so many nematicides have been phased out, or put under limited use mandates is that to be effective, they are required to spread via air spaces or water films to a depth of 1 metre or more in soil and must be chemically stable to moisture and heat; unfortunately this has meant they have often persisted and accumulated in the environment and can potentially contaminate ground water.

There is therefore a need to develop new, environmentally friendly nematicides with broad applicability and a low cost of production. Traditional approaches to pesticide and nematicide discovery have largely centred on screening (often proprietary) compound libraries and following up the hits with further screens and detailed analysis. Although, at considerable cost, this has achieved some success overall the approach has not produced the outcomes that the market seeks.

In 2012 Nemgenix commenced development of an integrated in silico pesticide discovery platform (known as “i-QUEST™”). This informatics driven approach is to screen in a step-wise fashion databases of bioactive small molecules (containing 2-D structures, calculated molecular descriptors (e.g. logP, molecular weight etc) and include known and predicted bioactivities into the selection process (the bioactivites include the affinity of the molecule for the target, pharmacology and ADMET data)). These descriptors are filtered by a series of proprietary models that reflect the specific absorption of compounds into nematodes (so they enter the target organism), chemical stability and biotransformation (so product life and environmental fate can be predicted), and synthetic accessibility rules (to select compounds that can be competitively priced for the market) The core data is abstracted and curated from the primary scientific literature and covers a significant fraction of the discovery of small molecule bioactive products. Those molecules which do not meet Nemgenix’s specific and proprietary selection criteria (relating to patentability, nematode biology and chemical properties e.g. bioaccumulation in the nematode, spread in the water film, persistence in the soil etc) are eliminated, resulting in a smaller subset of compounds which can then progress to the bioassay phase of the discovery process. These are screened using a range of relevant plant parasitic nematode species to generate leads for future optimisation, safety testing and development. Data derived from the screening process is then fed back into i-QUEST™ to further enhance the platform and optimize the unique filters. A key feature and advantage of i-QUEST™ is that screening is first undertaken on the entire known chemical space and the filtering process is undertaken very aggressively to hone in on nematicidal activity. This results in an enriched pool of nematicidal compounds for which further investment in terms of time and resources is warranted.