Very little blogging time today, but I wanted to throw a question out to the readership instead. I’m at the Keystone conference on Phenotypic Drug Discovery, so here’s a relevant topic: what are your own experiences with phenotypic screening?
Background for those outside the field: broadly speaking, you can sneak up on a drug by two big routes. If you have an idea of a particular target (protein, etc.) you can screen against it directly to see if you have compounds that affect it. That’s the target-based approach. The other way is if you have some assay in cells or animals that shows you improvement in a particular disease state, then you screen compounds on that and see if you find something that helps. If you find a compound, you of course have no idea about how it might work, but there are lot of interesting techniques to try to work backwards and learn something new about the biology (as well as moving towards a new drug). This is the phenotypic approach. There are a lot of ways to sort of be in between these two, but that’s the main point.
I’ll let everyone define phenotypic screening their own way (just mention what that might be), but I’m interested in how many people have been on phenotypic projects and how things worked out. I myself have never been on a pure phenotypic project, but I’ve seen them lead to clinical candidates in the labs right next door to me at different times. At the same time, I’ve also seen them consume a lot of time, effort, and money and not deliver (to be clear, you can say the exact same thing about target-based drug discovery).
My own contribution to the discussion is the observation that if the organization is not committed to making the final leap into the clinic based on the phenotypic model, then you shouldn’t have started the program in the first place. And that does happen. Every such project gets to a leap-of-faith point when you have to go into humans, and that’s when you discover how strongly you believed that phenotypic model in the first place. It would be better to experience that under less trying conditions, i.e. earlier in the program!