Covalent Fragment Screening with Chemoproteomics: KEAP1 Engagers with an Unusual Warhead

On Feb. 16, 12:00PM PST, Dr. Mira Pochon, Staff Scientist and Head of Translational Biology at Global Blood Therapeutics, gave a PBSS/CLSA webinar on one of 2019's drug approvals , voxelotor (GBT440).  Mira has been with GBT since it’s early days in 2011.  GBT’s chemistry team was led by their CSO Dr. Brian Metcalf, former head of drug [...]

KIN-3248 (Kinnate Biopharma) is a next-generation, irreversible, pan-fibroblast growth factor receptor inhibitor (FGFRi) in a first-in-human (FIH) dose-escalation study (NCT05242822) in adults with advanced tumors harboring FGFR2 and FGFR3 gene alterations. The program is an excellent case study for rational covalent drug design to address kinase mutations while maintaining sufficient PK properties for oral daily dosing in humans.

PF-07817883 (ibuzatrelvir) is an oral, second-generation SARS-CoV-2 M^pro inhibitor developed by Pfizer. These efforts follow the success of Pfizer's antiviral combination drug, Paxlovid, which was granted Emergency Use Authorization by the FDA for the treatment of COVID-19. PF-07817883 was granted Fast Track designation and recently completed a Ph. II clinical trial in outpatient adults with COVID-19 symptoms. This article details the discovery strategy for PF-07817883, which includes addressing metabolic soft spots identified through MetID studies, recent clinical developments, and more.

We asked the global drug discovery community to nominate and vote on their favorite molecule from 2021, and the results are in. The 2021 choice for Drug Hunter’s Small Molecule of the Year is Pfizer’s CoV-2 M pro Inhibitor, PF-07321332 (nirmatrelvir, Paxlovid) . Published in a November 2021 Science article , the molecule was praised for its [...]

In Wednesday’s Flash Talk webinar, we covered recent highlights in covalent drug discovery, with lots of great questions from the audience. The webinar and recording are available below to everyone thanks to our sponsor, Revvity Signals, and the slides are available for download to Premium members at the bottom.