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 …
When interpreting compound pharmacokinetic (PK) data, it’s helpful to have reference values to compare experimental data to. A compound with a measured rat clearance value of 0.3 L/hr/kg, for example, is being removed at a slow rate relative to rat liver blood flow (3.3 L/hr/kg), indicating that the compound is not rapidly metabolized or excreted …
Of the record 59 FDA drug approvals from 2018, the majority were small molecules (64%). Keep at it, chemists! 🙂 Oncology and infectious diseases were the areas with most small molecule approvals, followed by genetic/rare diseases. Some more statistics below. Last year the FDA approved a record 59 novel drugs, which included 38 small molecule …
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 »
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 »