Going all retro with drugs…July 29, 2016 by
Going all retro with drugs (but we’re not talking about the 70’s, this is 2016). You may have recently read recently about a technology called computer-aided synthesis design (CASD). The idea, which has been around since the 70’s, is to help chemists to figure out how to make molecules, say for example, a new drug, by “teaching” computers to understand chemistry. This is almost like when IBM “taught” Deep Blue to play chess and Google “taught” AlphaGo to play go. Now after reading these first sentences, I’ve no doubt that some of you are sitting there thinking that the idea of a computer being able to work out how to make molecules it is nice, but such a system probably isn’t possible, or if it is, it’s likely years away from maturity or it’ll only work well with simple molecules. However, I’m here to tell you that such a system is much more than experimental and is, In fact, already being used by some of the world’s largest chemical and pharmaceutical companies to solve their chemistry problems. It’s called Wiley ChemPlanner. To understand why this technology is so revolutionary, especially if you’re not a chemist, it’s first important to consider the process a chemist goes through to make a drug molecule. Generally a chemist will look at the structure of a molecule and use their training and experience to roughly identify which bonds could be made between which atoms and which reactions could be used. He or she would then trawl through published papers looking for examples of similar reactions with similar types of molecules and would do this reverse-engineering, or retrosynthesis, for the whole molecule. As you can imagine, the bigger the molecule, the more complicated this process becomes, and that’s before it gets to testing anything for real in the lab. Figuring out how to make molecules like this is one of the reasons that drug development is such a lengthy and expensive process. The search tools available to chemists today are very powerful and can search through millions of papers in seconds. Nevertheless, search results are limited to matching what a chemist knows or thinks might be possible with what has already been done. It’s well known that this leads development chemists to use a very small subset of the thousands of types of known reactions again and again, even though these may not actually be the safest, most economic, or most sustainable options for making the molecule. In contrast to conventional search tools, ChemPlanner uses clever chemoinformatics algorithms and hundreds of thousands of rules about how chemical reactions work to generate complete synthetic sequences for making molecules. But although that’s pretty good in itself, that’s not the best bit. The best bit is that based on all these algorithms and rules, ChemPlanner can actually predict reactions that should work to get you to your target. Do not adjust your safety specs, you read that correctly; predict. This means that even if neither the molecule nor any methods for preparing it have been reported in the literature before, ChemPlanner can help a chemist generate synthesis routes to it, starting from simple, commercially available starting materials, in a matter of minutes. You’ll also note the plural there, as in, not just one route, but it’s possible to generate tens and maybe even hundreds of possible ways to make a given molecule. If you were skeptical about any such system existing in the first place, then you’ll definitely be skeptical of a system that claims predictive power of anything, let alone an employee of the company that makes said system telling you how great it is (i.e., me). You want further explanation and proof, right? Well, as you might have noticed, this is only the first post on this blog so I’m not going to tell you everything in one go. If you want to know more, then keep watching, because we’ll be showing you how ChemPlanner works and some examples of what you can do with the most innovative chemoinformatics tool available in the next posts. If you don’t want to wait, then there’s a video you can watch about it here, or you can request a free private demonstration by webex and evaluation license for your company, because you’re more than welcome to test it for yourself!