2019 was another big year for novel drug approvals (48 in total) though it wasn’t the record year of 2018 (with 59). The overall explosion in biologic drugs / non-small molecule modalities continued with year with 14 novel biologic drugs, including 3 monoclonal antibodies, a recombinant fusion protein (Reblozyl), 3 ADCs, an siRNA drug (Givlaari), …
2019 was another big year for drug discovery, with 29 FDA novel drug approvals for small molecules[note]Including istradefylline which was first approved in Japan, but not including brilliant blue G, fluorodopa F18, Ga-68-DOTATOC, bremelanotide, afamelanotide, and ferric maltol, which could all be considered small molecules by some definitions: https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2019[/note] and 3 for antibody-drug-conjugates so far.[note]The …
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 thinks you have a better …
Kinase Inhibitor Types Predicted with Machine-Learning Read More »
Having a clinical drug-induced liver injury (DILI) signal is a surefire way to kill a drug candidate in non-serious indications like pain or chronic indications like diabetes, and will even give oncologists second thoughts as cancer patients are living longer. What can we do to prevent it? A widely accepted strategy for minimizing DILI risk …
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 have very similar binding pockets. Weak interactions such as Dunitz interactions, polarized C-H hydrogen bonding …
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 compounds …