Liver toxicity remains an unpredictable hurdle for medicinal chemists

Let’s talk about the liver, with the understanding that medicinal chemists and drug discovery folks in general are always ready to talk about it. We have what must be described as a wary relationship with the organ, because (thanks to the work of the hepatic portal vein) everything that makes it into the bloodstream after being ingested goes straight to the liver before it goes anywhere else. This includes our orally-dosed drug candidates, and the problem is that the liver is absolutely stocked with enzymes to tear such interloping compounds to bits. That’s ‘first pass metabolism’ in the lingo, and it can be a brutal process.