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 …
On Feb. 16, 12:00PM PST, I’ll be hosting Dr. Mira Pochon, Staff Scientist and Head of Translational Biology at Global Blood Therapeutics, for a PBSS/CLSA webinar on one of my favorite 2019 drug approvals, voxelotor (GBT440). Mira has been with GBT since it’s early days in 2011, and will be able to tell the whole …
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 …
BMS-986142 is a reversible BTK inhibitor with two axial stereocenters. BMS synthetic chemists were able to make >200 kilos of this compound as a single isomer using this route. Wow. Atropisomers are a nightmare in drug discovery. Axial stereocenters are not easy to set predictably, separation of isomers is a pain, and the products are …
Adventures in Atropisomerism: A Case Study from BMS Read More »
Checkpoint inhibitors like pembrolizumab (Keytruda) have revolutionized treatment for many late-stage cancer patients, including Jimmy Carter. Recently, Keytruda stunned the world again with efficacy in metastatic non-small cell lung cancer, the leading cancer killer. Here’s a summary of its recent successes and the surprising path Keytruda took through two acquisitions and the Merck “out-license” list. …