We asked the global drug discovery community to vote on their favorite molecule from 2020, and the results are in. The community’s 2020 choice for Small Molecule of the Year is GS-6207 (lenacapavir), the awe-inspiring HIV capsid inhibitor published by Gilead Sciences in a 2020 issue of Nature. The GSK RIPK2 PROTAC degrader received the …
This post briefly introduces chimeric molecules and companies working on them, contains a list of 10 recent “hot” papers in this field, and some predictions for where chimeras might head. It’s Chinese New Year time, which means a significant part of the global biopharma supply chain has ground to a halt, due to our colleagues …
We all knew process scientists were good, but the Merck and Codexis teams just took it to another level! Unnatural nucleosides like Merck’s reverse transcriptase inhibitor islatravir (1, Figure 1) are well-known to be challenging to synthesize by traditional methods, as evidenced by several published chemical syntheses of this molecule requiring a dozen steps or …
Merck/Codexis Magic: Biocatalytic Synthesis of Islatravir Read More »
The C-H — O hydrogen bond is so well established in structural biology today, that it’s been overlooked that the C-H — O hydrogen bond was first proposed by a woman, June Sutor, in a 1960’s Nature article.[note]Sutor, D. J. “The C-H … O Hydrogen Bond in Crystals.” Nature, 1962, 195, 68-69. https://www.nature.com/articles/195068a0.pdf[/note] Her commentary …
The global cancer immunotherapy pipeline continues to explode with nearly double the number of active targets in 2019 vs. only two years ago, comprising 3,876(!!) active drugs, with a subset undergoing >5000 active clinical trials. In 2016, I listened to Dan Chen, former Global Head of Cancer Immunotherapy Development at Genentech, comment on the challenge …
Scientists from GlaxoSmithKline’s Stevenage site have an excellent article in J. Med. Chem. showing that cyclopropyl pyran (CPP) groups can serve as viable isosteres to N-pyrimidyl morpholines thanks in part to favorable cyclopropane σ -> aryl π interactions. N-aryl morpholines are privileged motifs in drug discovery, and suitable hydrogen-bond accepting isosteres are scarce. This is …