Highlights - Drug Hunter

Where Do Recent Small Molecule Clinical Candidates Come From?

Modern hit-finding technologies are incredible. Dean Brown and Jonas Bostrom at AstraZeneca have a very nice review out summarizing the hit-finding strategies for 66 clinical candidates published from 2016-2017. Some highlights include a clinical candidate from DNA-encoded libraries at GSK, the discovery of an RNA-binding drug candidate by PTC/Roche, and fragment-based programs with candidates 100,000x …

Where Do Recent Small Molecule Clinical Candidates Come From? Read More »

Adventures in Atropisomerism: A Case Study from BMS

Case Studies, Chemistry, Highlights / By Dennis Hu

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 »

That Jimmy Carter Drug

Articles, Case Studies / By Dennis Hu

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. …

That Jimmy Carter Drug Read More »

A Trick to Fluorinate Grignards

Chemistry, Highlights / By Dennis Hu

Knochel’s group has shown that you can fluorinate Grignard reagents without decomposition via single-electron transfer reactivity (SET) by a simple solvent switch from THF to DCM. A common way to prepare aryl fluorides is through lithium-halogen exchange, followed by trapping with N-fluorosulfonimide (NFSI). This isn’t always viable, as the alkyllithium reagents used in the exchange …

A Trick to Fluorinate Grignards Read More »

The Post-Gleevec Era

Articles, Case Studies, Perspectives / By Dennis Hu

Gleevec (imatinib) was the first tyrosine kinase inhibitor approved for the treatment of cancer and one of the first products to emerge from “rational drug design.” It’s invention changed chronic myeloid leukemia from an incurable death sentence to a manageable disease. Here’s a look back on the tremendous value it’s created over the last two …

The Post-Gleevec Era Read More »