fbpx

molecules of the month

PF-06835919

first-in-class ketohexokinase (KHK) inhibitor

oral candidate in Ph. II for NAFLD/NASH

from frag.-based screening, SBDD, and opt.

J. Med. Chem., Sep. 27, 2020

Pfizer, Cambridge, MA / Groton, CT

Structure of PF-06835919
1 min read

PF-06835919 is an oral first-in-class clinical candidate for NAFLD/NASH targeting ketohexokinase (KHK), an enzyme which initiates the metabolism of fructose. The authors describe a very elegant structure-based design campaign to improve a modestly active, quickly cleared lead molecule into this highly potent, permeable, bioavailable, and metabolically stable candidate. Key to success included the displacement of a water molecule and removal of three(!) hydroxyl groups from the original lead. It’s interesting that the molecule contains both an azetidine and azabicyclohexane motif, features that were once rare but now seem to be increasingly found in clinical molecules.


request a trial

You don’t have time to read everything, but you can’t afford to fall behind.

Drug Hunter Premium is drug discovery, distilled, so you can quickly catch up and make informed decisions based on industry examples.

Get ahead now by requesting a trial.


already a member? log in: