Abuse of open access tools and data?

As in a previous blog of mine described, it is rather simple to set up virtual compound design from the comfort of your home. Tools and data are easily accessible and hardware is cheap. Add to that a bit more hardware, maybe even a (garage) laboratory – it makes you wonder “What If”?

Is it possible that open access data is abused for criminal purposes, in particular recreational drugs? I recon it it would make sense (unfortunately) and I am sure there are more articles to be found other than the one I stumbled upon recently, dating back to 2013, by the Guardian. Though they don’t give any source or example for their (probably legitimate, imho) claim of what/were “clandestine” labs are.

Synthesis of known (recreational) drugs have been accessible since the days of Usenet newsgroups (seen them myself back in the days) and probably even BBSs. And then there is of course PhiKal, perhaps one of the main sources for Usenet/BBS in those days, before internet became bigger and easier accessible. With that know-how also follows a list of how to replace certain ingredients with household items/chemicals as replacement of otherwise only laboratory accessible items. It is so simple nowadays, a simple Google search will yield e.g. the recipe for crystal meth based on household chemicals; “Breaking Bad” in real life.

Combine the urge do to something like this with knowledge on pharmaceutical design and open access…..

Though as long as as so called designer drugs seem to be based on arbitrary testing of only slightly modified existing compounds – one of many examples fitting that picture seems to be acrylfentanyl – it doesn’t look like  open access is the culprit (yet).  It’s more the usual greed and stupidity with as fast, simple and cheap turn-over as possible – health and safety concerns have never been on the agenda. The only optimization probably is accessibility of starting materials. If there is anything valid to the above mentioned article, then of course the synthesis can go beyond your local garage and is done by “professionals” with expert equipment and chemicals. But hey, maybe I am naive and there are pro-labs doing all the typical design and test cycles as a pharmaceutical company would do…. Not that that is a good justification for illegal drugs.

It’s a rather scary thought – I am not sure what, if anything at all, can be done about this.

Perhaps the law-makers should start banning substances based on their pharmaceutical action, or generic structure (Markush like?), rather than one-by-one. I believe a similar problem exists in the area of sports & doping, were new “undetectable compounds” turn up faster than anyone has time to analyze and make new laws prohibiting previously identified ones.

I (obviously) can only recommend against any type of creating existing or new drugs – not only from a substance abuse of legal issue, but also from a plain health perspective – putting untested “shit” into your body will lead to – shitty results, plain and simple.  And if you are not a chemist doing “shit” in your garage, well, count on “shit” happening.

SpotRM+ – potential reactive metabolite formations – batch analysis in Knime

Modelling and prediction of toxicity of drug compounds has been, is, and will be be a continuous area of interest. I won’t go into the detailed literature of this, here, I want to focus on SpotRM+’s contribution to that field:
This methodology focuses on reactive metabolite formation and avoidance as a means to reduce structure based toxicity issues. In addition, it is a computationally cheap method since it is solely based on SMARTS, carefully hand-curated ones at that. In addition to identifying certain structural features, SpotRM+ delivers one to three page monographs on the marketed (or withdrawn) reference compounds including mechanistic summaries. So it is more about learning than pure black box filtration.

SpotRM+ requires Bioclipse, a platform which has chemical data-mining in its focus. There is a disadvantage to this package – you can only run and analyze one compound at a time, batch mode isn’t possible.
According to the company Awametox AB, the batch mode analysis is a feature requested by a number of customers, e.g. for design/synthesis prioritization. And yes, it is possible – IF you use script based or workflow based tools with one of the simpler ones being Knime. For this, you require access to the SpotRM+ database itself and the standard chemistry mining nodes in Knime.
[note that SpotRM+ is a commercial package, though there is a free demo available; both are based on Bioclipse. For the mining suggested here you need the database itself which can be purchased separately]

One of the drawbacks of the database and the SpotRM+ system with regards to batch analysis is that it isn’t really designed for batch analysis. The readout usually consists of a traffic light colouring system of reference compounds and links to their analysis monographs. Thus, for batch mode to work, you need to ask what you desire of it -e.g.

  • Is a single “red” or “green” reference hit sufficient?
  • Do you want to summarize all the reference hits?
  • Combine with other data for further calculations?

In principle, anything goes, that’s the beauty of the flexibility of a package such as Knime. But, would that be sufficient for you to make a decision? I can imagine that a batch based “high quality” decision should be possible, if you combine the output with, e.g., a model based on measured ADMET data (and/or reactive metabolite data).
Independent of the latter, a basic workflow could look simply like this:


You can find more info and access to mentioned programs here:
SpotRM+:   www.awametox.com (bioclipse included; recently updated to V1.2!)
Bioclipse:   www.bioclipse.net (mainly for info, not required to download separately)
Knime:   www.knime.org