Small-molecule drug candidates are increasingly falling “ beyond the rule of 5 ,” making oral administration more challenging. Optimizing a drug’s solid form can improve its solubility and bioavailability when further molecular modifications are prohibitive. This minireview covers solid form strategies for increasing the solubility and oral [...]
This article explains what LogD is, why LogD (or LogP) is important in drug discovery, rookie mistakes in drug discovery that come from overlooking LogD or LogP, and contains a LogD reference poster that shows the estimated amount of potency attributable to lipophilicity considerations alone. By Dennis Hu Jump to Cheat Sheet Lipophilicity is [...]
Medicinal chemists often face cardiotoxicity issues linked to inhibition of the hERG (human ether-à-go-go-related gene) channel. In a recent Coffee Chat, Drug Hunter CEO Dennis Hu, Director for Industry Research and Relations Dennis Koester, and Senior Scientific Editor Matt Hesse discussed ways to reduce hERG risks during lead optimization. They described approaches to reduce hERG affinity while retaining on-target potency and discussed case studies of drug programs that used these strategies to eliminate their hERG issues.
You’ve probably lived this story before: you’re working on your favorite kinase, YFK1, and are looking for selective inhibitors over YFK2. The problem is, they’re virtually identical near the active site, save for a single residue sitting in the back pocket that your amazing structural biologist has identified. The team [...]
This article introduces the Topliss tree and Topliss schemes for analog synthesis, illustrates when they might be useful, and provides easy-to-use posters or "cheat sheets" of the original schemes. By Christian Kuttruff Why are the Topliss Tree and Topliss Schemes Useful? Imagine you’re on a new project that has just conducted a chemical [...]
