AZ13767370 (Compound 13)
Mechanism of action: Covalent Erk1/2 inhibitor
Compound 13 inhibits Erk2 with a potency of 0.0069 (Km ATP, 120µM) and 0.0085µM (1mM ATP concentration) in a biochemical RapidFire Mass Spectrometry assay.
In cellular assays using an A375 cell line (b-RAFV600E mutation), compound 13 inhibits pERK and pRSK with an IC50 of 0.022 and 0.065µM respectively.
The covalent mechanism action of this series was confirmed through x-ray crystal structures, mass spec studies and time-course cellular assays.
Suitable for and exclusions
Restricted to preclinical oncology studies (proposals) only. The compound would make an ideal in vitro tool compound, with the potential of being an in vivo mouse probe if co-dosed with ABT (see publication for details of mouse PK).
Publications for this compound
Find out more about this compound by reading related Publications:
Journal of Medicinal Chemistry
Structure-Guided Design of Highly Selective and Potent Covalent Inhibitors of ERK1/2
Gene information from the NCBi
This compound works on the following genes: