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.

The 2024 edition of MCR (Medicinal Chemistry Reviews), edited by Joachim Rudolph and Will Watkins, has just been published by the American Chemical Society MEDI Division. Featuring contributions from a global team of section editors and authors, MCR offers concise updates on a broad range of contemporary drug discovery topics, making it an invaluable resource for both aspiring and experienced medicinal chemists.

Nurix’s NX-2127 is an orally bioavailable BTK degrader that exhibits in vivo degradation across species and has advanced into first-in-human clinical trials for relapsed/​refractory B-cell malignancies. This molecule one-pager serves as a reference guide, offering an overview of the scientific significance of Nurix's NX-2127 program. It includes links to key presentations, publications, patents, preclinical and clinical PK data summaries, and more.

Arvinas’ ARV-471 is an orally bioavailable CRBN-based ER PROTAC degrader for treating patients with ER+/HER2-breast cancer and the first PROTAC to enter Ph. III clinical trials. This molecule one-pager serves as a reference guide, offering an overview of the scientific significance of Arvinas’ ARV-471 program. It includes links to key presentations, publications, patents, preclinical and clinical PK data summaries, and more.

The INN Proposed List 131, released on August 11th, 2024, unveils the latest batch of drug names currently under consideration by the WHO. To streamline your review, we’ve distilled and compiled a searchable table for the small molecules that includes company identifiers, the newly proposed drug names, structural information, original patents, companies, and mechanisms of action, including structures that were previously undisclosed.

Kymera's KT-474 is the first oral heterobifunctional degrader to demonstrate activity in clinical trials outside cancer. This molecule one-pager serves as a reference guide, offering an overview of the scientific significance of Kymera's KT-474 program. It includes links to key presentations, publications, patents, preclinical and clinical PK data summaries, and more.

As part of our "Molecules of the Month" and "Molecule Roundup" series of articles, which bring you the most interesting drug discovery molecules published each month, by member request, we have brought together recently highlighted molecules into a single searchable table. This tool allows you to see longer term-industry trends in therapeutic areas, target selection and chemical matter to inspire ideas for your drug discovery pipeline.

As part of our series of monthly patent roundup articles, which bring you highlights of the most relevant drug discovery IP disclosures, by member request we have collated recent selections into a single searchable table. This tool allows you to see longer-term industry trends in therapeutic areas and target selection to inspire ideas for your pipeline.

Understanding how a small molecule ligand binds to its target is valuable in drug discovery, because it enables more efficient optimization through structure-based design, better mechanistic understanding of molecular pharmacology, and greater confidence in the therapeutic hypothesis from both safety and efficacy perspectives. Recently, Drug Hunter highlighted methods for target identification when the target is unknown.

Targeted Protein Degradation (TPD) allows for elimination, rather than inhibition, of proteins by exploiting cells’ own protein clearance mechanisms. While traditional inhibitors can be very effective at preventing a protein from undertaking a particular function, blocking protein activity...

How a Follow-on Drug Can Create Value After a First-in-Class Drug Novel drugs can make a big impact in two main ways—by being first-in-class (FIC) or by being best-in-class (BIC). A novel drug that produces its therapeutic effect by interacting with a new target or that is used to treat a new condition is considered first-in-class (FIC) [...]

Optimizing lead compounds to have drug candidate-like qualities is time-consuming and expensive. Oftentimes, critical drug discovery project questions, such as on-target pharmacology or toxicology, can be answered more efficiently with compounds that are "good enough," saving teams time and further resource investment. This article discusses [...]

Dear Drug Hunter, It's gotten harder and harder to keep up with everything that's going on in the industry. From new company launches to drug approvals, endless publications to regulatory updates, the volume of information drug discovery leaders need to make good decisions seems endless. Our mission is to save you time by curating industry [...]

Learning from industry leaders is one of the best ways to grow as a drug discovery professional. This table lists some of the top drug discovery blogs and biopharma social media influencers, all of whom are clearly passionate about their work. These are excellent, free resources that offer valuable insights and perspectives.

It's hard not to think about infectious diseases at the moment, but it's a great time to review the drug discovery literature. One area of drug discovery that has deep roots in infectious disease research is targeted covalent inhibition. Targeted covalent inhibitors form covalent bonds with discrete targets (as opposed to [...]

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 [...]

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 [...]

This table features a selection of some of the best drug discovery journals. While not exhaustive (our team’s RSS feed includes hundreds), this is a subjective list of where to find the most valuable articles for those entering the field.

This table features a selection of some of the best books on drug discovery, as well as related topics such as pharmacology, toxicology, pharmaceutics, and biotech. While nothing can replace hands-on industry experience, a few books serve as valuable references and offer insights into the realities of drug discovery. We recommend this list as a useful technical resource or as an informative introduction to the broader field of drug discovery, beyond any single discipline.

This table contains a list of some of the best drug discovery websites, online databases, and other online resources for drug hunters everywhere. If you have a suggestion for websites that we may have missed, let us know!

Protein-ligand interactions are driven predominantly by strong hydrogen-bonding interactions, de-solvation energetics, and other entropic considerations including ligand lipophilicity. However, the combination of many weaker interactions can contribute to potency, and are often necessary to obtain selectivity when targets and anti-targets [...]

With the biochemistry magic available to the liver, it's a wonder that anything we consume is well-tolerated. Even carboxylic acids are structural alerts as they can be converted to bioreactive acyl glucoronides. The best we can do as drug hunters is minimize the risk of toxic metabolite formation and apply assays appropriately to select [...]

There are catalysis geniuses (looking at you, process chemists!) and then there are those of us just looking to put compounds in vials.  Here are the simplest conditions that'll get you what you want 90% of the time.  Beyond that you'll need to ask a guru like Nick White or Malcolm Huestis. Hope this table helps. Explore drughunter.co m for more.